Biomedical subjects
Publications and source records attributed to R P Kitching.
Foot and mouth disease (FMD) in cattle is usually clinically obvious in the unvaccinated herds of countries in which the disease occurs only occasionally. However, in vaccinated herds and in some breeds indigenous to areas in which FMD is endemic, the disease may circulate undetected.
Countries that are free of foot and mouth disease (FMD) are reluctant to use vaccine in the event of an outbreak because of the difficulties this can cause in re-establishing freedom from FMD status to the satisfaction of trading partners. The problem does not lie in distinguishing between vaccinated and recovered animals as vaccinated animals can be tagged or otherwise marked to show that they have been vaccinated; the difficulty is in identifying vaccinated animals that have had contact with live virus and become carriers. The traditional probang test is not sufficiently sensitive and is labour- and laboratory-intensive, but alternative serological tests such as those for antibodies to non-structural proteins (NSPs), or specific immunoglobulin A (IgA) are also not 100% sensitive. However, these newer tests do provide increased security by reducing the likelihood of trading carrier animals and can be used to help define the limits of an outbreak; the use of vaccine to help control an outbreak of FMD in a previously free country still has significant consequences on trade in FMD susceptible animals and their products.
In intensively reared pigs, the introduction of foot and mouth disease (FMD) results in severe clinical disease and vesicular lesions in adult and fattening animals, and high mortality in piglets. Vaccination of uninfected herds can assist FMD control and eradication programmes by reducing susceptibility of pigs older than 12 to 14 weeks and providing early protection to piglets through maternal antibody, but once FMD is established on a farm, vaccination alone will not prevent recurrent outbreaks of clinical disease.
The recent outbreaks of foot and mouth disease (FMD) in Argentina, Europe, Japan, the Republic of Korea, South Africa and Uruguay have brought to world attention the devastating effects of the disease in a naïve population and the social and economic costs of control and eradication. The fact that much still remains unknown about the natural history of FMD virus came as a surprise to some. This paper attempts to identify where research should be directed in order to be better prepared in the future.
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Aedes aegypti female mosquitoes are capable of the mechanical transmission of lumpy skin disease virus (LSDV) from infected to susceptible cattle. Mosquitoes that had fed upon lesions of LSDV-infected cattle were able to transmit virus to susceptible cattle over a period of 2-6 days post-infective feeding. Virus was isolated from the recipient animals in 5 out of 7 cases. The clinical disease recorded in the animals exposed to infected mosquitoes was generally of a mild nature, with only one case being moderate. LSDV has long been suspected to be insect transmitted, but these findings are the first to demonstrate this unequivocally, and they suggest that mosquito species are competent vectors.
Nine isolates from pigs persistently infected with a recent Italian isolate of swine vesicular disease (SVD) virus, ITL/9/93, were collected sequentially over 121 days and were characterized antigenically and biochemically. There was an accumulation of amino acid (aa) substitutions in the capsid proteins throughout the carrier state that could be correlated with alterations in antigenicity in virus isolates collected late stage in infection. The aa substitutions detected mainly occurred in VPI and antigenic changes were detected in late isolates both at antigenic site 1, resulting in loss of binding of Mab 4GO7, and at a closely located site which has not yet been named, recognized by Mab C29. In further experiments groups of pigs were exposed to a range of SVD viruses, but no virus was isolated beyond 16 days post infection (dpi) nor viral RNA detected beyond 42 dpi. Attempts to transfer infection to sentinel pigs introduced some time after initial infection of the original pigs were largely unsuccessful. The carrier state was established in only one out of five experimental infections of pigs with SVD virus and can therefore be considered a rare sequel toinfection with SVD virus and is of limited significance in the epidemiology of the disease.
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Partial nucleotide sequence at the 3' end of ID (VP1-encoding) gene of 90 foot-and-mouth disease virus type O isolates recovered from field outbreaks in India between 1993-9 were determined. The sequences were compared with each other and reference viruses. The published sequences of 15 type O isolates recovered from different parts of Asia and one isolate (O1BFS) from Europe and one from Egypt (O1/Sharquia/Egypt/72) were also included in the analysis for comparison. On the basis of phylogenetic analysis the viruses could be grouped into four distinct genotypes (genotypes I-IV). All 90 isolates from India were genotype-I, as were the reference isolates from Bangladesh, China, Egypt, Iran, Saudi Arabia, Syria and Turkey. Genotype-I isolates were further subdivided into 16 sub-genotypes. The Indian isolates were found to be extremely heterogeneous in nature and clustered into 12 different genetic groups. In genotype-I, the nucleotide sequence difference seen between the isolates was 0-11.6%, while among the Indian isolates it is 0-8.8%. Viruses of similar genetic groups are circulating in India, Bangladesh and countries of the Middle East. Genotype-II and -III are represented by isolates from Lebanon (O1/South Lebanon) and Europe (O1-BFS), respectively. Genotype-IV is formed by isolates from China, Hong Kong and Taiwan. The present study reveals the occurrence of viruses belonging to multiple genetic groups over a short period of time and persistence of single genetic group in the same geographical area over several years. This is consistent with the endemic nature of the disease in the country.
Transmission of foot-and-mouth disease virus (FMDV) by aerosol spread can occur over considerable distances. However, this is less effective in hot, dry environmental conditions, and a detailed study of an outbreak within a large dairy herd in Saudi Arabia has shown that contact spread is the main mode of transmission within a herd: both physical and spatial barriers curtailed the course of disease across the farm. Hence, the speed and path of an outbreak can be altered by changing the positioning of spatial or physical barriers. Extending the distances between pens, increasing the number of farm pens, decreasing the number of animals within the pens, and placing pens of well-protected stock between those of susceptible stock, can all contribute to the control of FMD involving contact and short-distance aerosol spread. Such management techniques offer a cost-effective supplement to control by vaccination.
Nucleotide sequence of the structural protein-encoding region of foot-and-mouth disease virus (FMDV) A22-India 17/77 was determined using non-radioisotopic technique. Comparison of nucleotide and deduced amino acid sequence with A22-Iraq 24/64 revealed 175 synonymous (silent) and 42 non-synonymous nucleotide changes resulting in 34 amino acid substitutions along the capsid proteins (VP1-VP4). Out of the 4 structural proteins VP4 is highly conserved. The highly variable and immunodominant protein VP1 showed 47% of the total amino acid substitutions. VP2 and VP3 contain 38.2% and 14.7% of the amino acid substitutions, respectively. The VP1-based phylogenetic analysis of 18 different type A viruses including A22-India 17/77 divided them in to two broad genetic groups (Asian and European/South American), and each group is further subdivided in to two separate genotypes. A22-India 17/77, A22-Iraq 24/64 and A22-Azerbaijan/65 formed one genotype and the 4 Chinese strains formed a separate genotype in the Asian group of viruses. In the European/South American group, A-Argentina/87 represents one genotype and the remaining 10 strains formed the second genotype in this group.
Swine vesicular disease (SVD) is a notifiable viral disease of pigs included on the Office International des Epizooties List A. The first outbreak of the disease was recognized in Italy in 1966. Subsequently, the disease has been reported in many European and Asian countries. The causative agent of the disease is SVD virus which is currently classified as a porcine variant of human coxsackievirus B5 and a member of the genus enterovirus in the family picornaviridae. From a clinical point of view, SVD is relatively unimportant, rarely causing deaths and usually only a minor setback to finishing schedules. However, the clinical signs which it produces are indistinguishable from those caused by foot-and-mouth disease, and its presence prevents international trade in pigs and pig products. This article reviews recent findings on all aspects of the virus and the disease which it causes.
World Trade Organisation agreements have swept aside many of the previous constraints to international trade in animals and animal products and have looked critically at those that still survive. The presence of disease, in particular the OIE list A diseases, still provide legitimacy for barriers to trade, and as a consequence the importance of reliable animal disease surveillance has increased. However, the economic consequences of reporting the occurrence of a List A disease have also increased, as this provides trading partners with sufficient reason to impose an embargo that could severely compromise the national agricultural industry. The dilemma for some developing economies, reliant on agricultural exports, is how to balance a transparent and efficient disease reporting service, sufficient to provide the necessary information for importing countries to make realistic risk assessments, with the perceived political damage from being honest with trading partners who might take advantage of the information to require additional safeguards and health certification.
The World Reference Laboratories for Foot-and-Mouth Disease and for Rinderpest provide a worldwide diagnostic and surveillance service for these disease for FAO and OIE. Both laboratories are housed within the high security facility of the Institute for Animal Health, Pirbright, UK. Foot-and-mouth disease (FMD) and rinderpest (RP) are OIE List A diseases and historically have caused huge losses to agricultural economies around the world, prompting the establishment of veterinary colleges in Europe and environmentally controversial control programs in Africa. FMD and RP have now been geographically restricted, but the large legal and illegal world trade in live animals and animal products constantly threatens to allow them to spread back into disease-free areas. The Reference Laboratories provide a center of excellence for the development of improved diagnostic techniques and a repository of isolates collected over many years. These libraries provide material for investigations of the molecular epidemiology and evolution of the viruses and a data base against which new isolates can be compared. Thus it is possible to individually characterize new outbreak strains, identify their likely origin and provide the most up-to-date support for their control.
Foot-and-mouth disease (FMD) has increased in significance as a major constraint to international trade in live animals and animal products as the World Trade Organization agreements remove other obstructions. A consequence will be reluctance to immediately declare the presence of FMD if it is thought possible to quickly eliminate its presence and so avoid trade embargoes. This will predispose to spread of disease between trading partners. In addition, as countries tend to increase the requirements for testing and certification of imported animals with the objective of reducing the risk of importing disease, the increased costs and delays that this involves will encourage the illegal trade and therefore have the converse result.
Foot-and-mouth disease (FMD) is a highly contagious virus infection of sheep, goats, cattle, pigs and other, non-domesticated species of artiodactyls, and causes both clinical and subclinical infection according to the natural or acquired immunity of the host. Within vaccinated dairy herds FMD may appear as an acute, mild or subclinical infection, dependent upon the immune status of the herd, the level of challenge and the efficacy of the vaccine used. In the large dairy herds of Saudi Arabia, sub-clinical FMD was on a number of occasions, found to have spread amongst the cattle before signs of disease were seen. Such undetected transmission resulted in a large incidence on the first day of diagnosis and curtailed the impact of post-outbreak vaccination (PoV). First day incidence (FDI) for these herds was found to correlate with the final cumulative incidence of clinical disease. Since FDI is available at the start of an outbreak it can be used as a predictive tool for the eventual outcome of an FMD outbreak. During the past 11 years 47 % of dairy herds examined in Saudi Arabia have experienced FMD initially as sub-clinical disease. For the remaining 53 %, waning vaccinal protection did not suppress clinical disease in the initially infected animals, and these showed severe rather than mild signs. Hence, in such herds there was a very low initial level of subclinical infection, so PoV was more effective, and the timing of PoV was found to give a good correlation with cumulative herd incidence: an early PoV resulted in low prevalence of clinically infected animals whilst late PoV permitted high prevalence. PoV timing can thereby be used in tandem with FDI as a predictive tool for future outbreaks, estimating the final cumulative incidence (or prevalence) of clinical FMD cases.
Six neutralizing monoclonal antibodies (MAbs) were used to isolate MAb neutralization-resistant (MAR) mutants from a recent European strain of swine vesicular disease virus (SVDV), ITL/9/93. Sequencing of MAR mutants identified two epitopes located at positions analogous to sites 2A (VP2) and 3B (VP3) on poliovirus (PV) which have been previously identified on a Japanese strain of SVDV. A third epitope near to the C terminus of VP1, not previously recognized on SVDV, was tentatively identified in a region analogous to site 1 of PV. A fourth epitope, located in the C-terminal region of VP3, has never before been recognized as a site of neutralization on picornaviruses. All four epitopes were predicted to be surface-exposed.
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