Search PubMed⌕ Search

Biomedical subjects

A I Donaldson

Publications and source records attributed to A I Donaldson.

At least 37 records · Page 2Linked to original sources

Development of a novel real-time RT-PCR assay for quantitation of foot-and-mouth disease virus in diverse porcine tissues.

Pigs are more difficult to immunise and more variable in their response to foot-and-mouth disease (FMD) than other livestock species. This has important consequences for FMD control during both prophylactic vaccination programmes in endemic situations and when emergency vaccination may be used as an adjunct to stamping out during outbreaks in countries normally free from the disease. The rapid and effective control of FMD in pigs is especially important in regions of high pig density since infected pigs have the potential to generate plumes of airborne virus and spread infection beyond the immediate control area. Increased knowledge of the kinetics of FMDV replication in pigs, especially in their respiratory tracts, could create opportunities for strategies to improve FMD vaccines for pigs. A fluorogenic TaqMan RT-PCR assay specific for the IRES (internal ribosome entry site) sequence of the O(1) Kaufbeuren/Lausanne strain of FMDV has been developed for this purpose. The assay had a sensitivity of 0.1 TCID(50)/ml, and a dynamic range of at least eight orders of magnitude. It was found that an established method of quantitation, relative to a housekeeping gene, exhibited two significant shortcomings when applied to a set of 16 anatomically highly diverse solid tissues: (i) tissue differences in housekeeping gene expression caused errors of up to 60-fold in estimated FMDV concentrations; and (ii) variability in total RNA yields caused unpredictable saturation of RT reactions, which in turn caused errors of up to 250-fold in the estimated FMDV concentration. A novel quantitation strategy, designated the C(t)(min) method, was developed to overcome these problems. The C(t)(min) method was based on the the RT-PCR examination of a dilution series of spectrophotometrically quantitated total RNA, spanning the optimum for the RT-PCR system used. The new method was influenced minimally by any tissue-specific RT-PCR inhibitors and was used to determine FMDV concentrations in tissues from four experimentally infected pigs. The results suggest that the lungs play a less important role in the replication of FMDV in pigs than was thought previously.

Animals↗

Protection of cattle against rinderpest by intranasal immunisation with a dry powder tissue culture vaccine.

Dry powder tissue culture rinderpest vaccine containing 10(2.5) TCID(50) of virus per dose administered intranasally to cattle induced high titre circulating antibody responses and protection against challenge with a virulent strain of rinderpest virus. A reduction in the dose of virus to 10(1.1) TCID(50) resulted in a failure to elicit detectable antibody responses and a lack of protection. Intranasal powder vaccine offers several advantages over conventional needle-administered aqueous rinderpest vaccine, including greater stability in the absence of a cold chain, reduced risk of 'needle transfer' of other microbial agents present in the vaccinated herd and lower cost.

Administration, Intranasal↗

An integrated model to predict the atmospheric spread of foot-and-mouth disease virus.

The application of a computer model called Rimpuff for simulating the airborne spread of foot-and-mouth disease (FMD) is described. Rimpuff is more sophisticated and accurate than other FMD simulation models previously described. It can be run on a desktop computer and performs analyses very quickly. It can be linked to a geographical information system and so the information generated can be integrated with geographical and demographical data for display in a format that can be easily assimilated and transmitted electronically. The system was validated using historical data from outbreaks of FMD in France and the UK in 1981, and from Denmark and the former German Democratic Republic (GDR) in 1982. A very good fit was obtained between the direction of the plumes of virus simulated by the model and the spread of disease from France to the UK in 1981. Although cattle in the UK were infected during the episode, the concentrations of airborne virus in the plumes simulated by the model were beneath the infectivity threshold for cattle. It was concluded from the analysis that the number of pigs infected in France, and therefore the source concentration of airborne virus, was probably much higher than was recorded at the time of the outbreaks. Analysis of the Denmark/GDR episode pointed to the possibility that the source of virus for the 1982 epidemic in Denmark could have been one or more unreported outbreaks involving pigs in the former GDR.

Animal Husbandry↗

Risks of spreading foot and mouth disease through milk and dairy products.

A review of epidemics of foot and mouth disease (FMD) has highlighted the important role which raw (untreated) milk can play in the spread of the disease in a country which is normally free of FMD and whose cattle are not routinely vaccinated. The greatest hazard is likely to be in the early stages of an outbreak, before disease control measures have been implemented. The spread of FMD through milk can be prevented by the effective application of control measures combined with 'codes of practice' for the treatment of potentially infected milk. The author considers the probable mechanisms of transmission of FMD by milk and dairy products. These mechanisms are based on the quantities of virus excreted in milk, the survival of the virus under various management and manufacturing conditions and the minimum doses required to initiate infection in susceptible animals by different routes. The key points for consideration when making a risk assessment of the importation of milk and dairy products are also discussed.

Animals↗

Research and technological developments required for more rapid control and eradication of foot and mouth disease.

Foot and mouth disease (FMD) is the major disease barrier to international trade in animals and animal products. Countries free of the disease take severe measures to exclude the virus, to avoid the potentially devastating consequences of an outbreak, particularly for the animal export trade. Consequently, FMD-free countries either refuse to trade with sporadically or endemically infected countries, or else apply stringent and often expensive safeguards before agreeing to import animals or animal products. Technological advances can assist countries which are free of FMD to maintain this status. Such advances also aid countries in which the disease is sporadic or endemic, by accelerating the progress of control and eradication programmes. The authors review recent advances in tests for the diagnosis of FMD, in addition to advances in surveillance, vaccinology and information technology, i.e. computing and networking. Furthermore, the authors examine the application of these advances to improve programmes for the control and eradication of FMD, and identify the requirements for further research into the disease.

Animals↗

Ultrastructural and replicative features of foot-and-mouth disease virus in persistently infected BHK-21 cells.

Persistent foot-and-mouth disease (FMD) virus infection in vitro has been studied in a chronically infected cloned BHK-21 cell line. Virus growth during serial cell passages was followed by infectivity assay and immunocytochemical staining. Only a small percentage of cells (0.006-6%) was found to harbour virus during persistence. Light and electron microscopy showed the presence of cytoplasmic protuberances ("blebs") at the surface of persistently infected cells. The curing of cell cultures was achieved by passaging them in the presence of polyvalent immune serum. The absence of virus in cured cells was confirmed by infectivity assay and immunocytochemistry. This finding, together with the low percentage of infected cells in cultures confirms that persistently infected BHK-21 cells satisfy the definitions of a carrier culture. The characteristics of the in vitro system and its relevance to the study of FMD carrier state in vivo are discussed.

Animals↗

Haptoglobin response of cattle infected with foot-and-mouth disease virus.

Haptoglobin, a major bovine acute phase protein, was evaluated as a marker of the primary replication of foot-and-mouth disease virus in 12 naturally infected cattle from which blood was collected daily. An acute phase response, as measured by an increase in serum haptoglobin concentration and the presence of fever, was not detected during the previraemic stage of disease, but there was a significant increase in serum haptoglobin after the onset of viraemia. It occurred on the same day as the first appearance of clinical signs in three of the cattle, one day later in four and two days later in the other five cattle.

Animals↗

Improved detection of persistent foot-and-mouth disease infection in cattle by the polymerase chain reaction.

Persistent foot-and-mouth disease (FMD) infection of cattle was established by exposure to infected pigs. Oesophageal-pharyngeal fluid samples collected ante-mortem and tissue samples obtained post-mortem were tested for virus by conventional means and for viral RNA by the polymerase chain reaction (PCR). The results showed that the PCR was superior for detecting the carrier state in tissue samples. A high neutralising activity in tissues probably influenced the yields of virus obtained by infectivity assay.

Animals↗

Detection of foot-and-mouth disease virus RNA in clinical samples and cell culture isolates by amplification of the capsid coding region.

Foot-and-mouth disease is one of the most economically important virus diseases of livestock. Two important requirements for the control of this disease are rapid laboratory diagnosis and epidemiological investigation. The use of the polymerase chain reaction method (PCR) to amplify specific nucleic acid regions offers the unique possibility of combining swift viral detection with the production of genetic material suitable for sequencing and other methods of molecular epidemiological analysis. The sequencing of the region of foot-and-mouth disease virus (FMDV) genome encoding the capsid proteins of the virus (approximately 2260 bps), provides valuable information that adds to the molecular characterisation of an isolate. This paper describes the use of the PCR for the amplification of this region of the FMDV genome from bovine clinical samples and cell culture isolates. Suitable pairs of oligonucleotide primers were selected from the published sequence of FMDV type O1, Kaufbeuren. One primer set amplified 2091 bps of the capsid coding region of all seven serotypes of FMDV. The other primer set amplified 216 bp from this region of FMDV type O1, BFS 1860, in nucleic acid extracts from several clinical samples. Nucleic acid extracts from the picornaviruses, bovine enterovirus and swine vesicular disease virus, which affect the same animals, were not amplified. Direct sequencing was carried out on the amplified fragments and showed that the PCR products were > 98% homologous to published FMDV sequences.

Animals↗

Foot-and-mouth disease: the risk for Great Britain after 1992.

Mass annual vaccination against foot-and-mouth disease, previously applied by eight member states in the European Community (EC), was progressively phased out during 1990-91. The other four member states (the United Kingdom, Denmark, the Republic of Ireland and Greece) either never have vaccinated or ceased to do so several years ago. The EC should increase its international competitiveness if it maintains its present foot-and-mouth disease-free, non-vaccinating status. Freedom from disease and a harmonised disease control policy will also permit unrestricted movement of livestock and animal products throughout the EC when the single market is completed in 1992. Vaccination against foot-and-mouth disease on continental Europe has greatly reduced the number of outbreaks during the last 30 years and this reduction has been of indirect benefit to Great Britain. However, the cessation of vaccination will result in a higher proportion of fully susceptible cattle and in the event of outbreaks will increase the likelihood of the rapid dissemination of virus and increase the risk that the infection will enter Great Britain. The main risks of entry are likely to be associated with live animals in which the disease can be mild or inapparent, ie, sheep and goats, and with airborne virus originating from pigs on the nearby continent especially in Brittany and the Benelux countries where they are present in very high densities.

Animals↗

A review of foot and mouth disease in Nepal.

Foot and mouth disease (FMD) causes substantial economic losses to the predominantly agricultural community of the Kingdom of Nepal. FMD is endemic in the country and four of the seven serotypes of FMD virus have been isolated (O, A, C and Asia 1). The epidemiology of FMD and the factors which play a role in its prevalence and spread are outlined. The National Epidemiological Laboratory for FMD has been established in Kathmandu and its diagnostic capabilities and activities are described. The important points to be considered in the formulation of any future regional or national control programme for FMD in Nepal are discussed.

Animals↗

The World Reference Laboratory for Foot and Mouth Disease: a review of thirty-three years of activity (1958-1991).

The range of activities and contributions of the World Reference Laboratory for Foot and Mouth Disease in Pirbright, Surrey, United Kingdom, from 1958 to 1991 is reviewed. The countries for which a service has been provided, the number of samples submitted for investigation and the serotypes identified are recorded. Factors which have influenced the number of samples received are outlined. The developments and improvements made in the laboratory diagnosis of vesicular virus diseases over the thirty-three-year period are described.

Animals↗

Foot-and-mouth disease virus strains isolated from persistently infected cell cultures are attenuated for mice and cattle.

It was previously reported that during serial passage of a BHK-derived cell line persistently infected with foot-and-mouth disease virus, (termed C1-BHK-Rc1) the virus became increasingly more virulent for BHK-21 cells (de la Torre et al 1988). Virus strains isolated from different cell passage levels were tested for virulence in mice and cattle. The results showed that in the course of persistence in BHK cells, FMDV became progressively less virulent for mice and cattle.

Animals↗

Transmission of foot-and-mouth disease by vaccinated cattle following natural challenge.

Cattle vaccinated with a conventional monovalent type O1 foot-and-mouth disease (FMD) vaccine were challenged between four and 21 days after vaccination by short-term exposure to homologous airborne virus produced by pigs. Transmission was then assessed by housing susceptible cattle with the vaccinated animals and testing and observing all the animals for signs of infection and clinical disease. All 18 cattle vaccinated three weeks before challenge resisted clinical disease and although four contracted subclinical infection, there was no transmission to susceptible cattle in contact. One of the two groups of cattle vaccinated two weeks previously transmitted subclinical infection, but not disease, to susceptible animals housed with them from day 0 after challenge. Subclinical infection was manifested by a transient viraemia which was not followed by a detectable circulating antibody response. Shorter periods (seven or four days) from vaccination to challenge resulted in transmission of disease from clinically normal vaccinated to in-contact animals in one of two experiments. The severe challenge presented by the diseased in-contact animals than overwhelmed the immunity of the vaccinated animals. The results indicate that during emergency vaccination programmes it is advisable to vaccinate all FMD-susceptible animals within the vaccination zone and that at the outer boundary of the zone vaccinated animals should be kept separated from unvaccinated animals for at least three weeks.

Animals↗