Foot and Mouth Disease

Current Perspectives

Francisco Sobrino, Esteban Domingo, Francisco Sobrino, Esteban Domingo

• Éditeur: CRC Press
• Année: 2019
• ISBN:
  9780429525131
• Édition: 1
• Sujet: Médecine
• Sous-sujet: Médecine vétérinaire

The shock following the recent outbreak of foot-and-mouth disease (FMD) in the UK dispelled the notion that this disease was permanently under control and could be forgotten. FMD proved to be an endemic disease in many countries and continues to pose a major threat to animal health worldwide. The development of more effective and socially acceptabl

Chapter 1

Stepping Stones in Foot-and-Mouth Research: A Personal View

F. Brown

Abstract

The history of foot-and-mouth disease falls into several distinct areas. 1. Loeffler and Frosch’s landmark description in 1897 that the disease is caused by a filterable agent, the first observation that an animal disease could be caused by a virus. 2. The search for experimental laboratory animals, culminating in the demonstration by Waldmann and Pape of the susceptibility of the guinea pig in 1920 and the suckling mouse by Skinner in 1951. 3. The discovery of three distinct serotypes O, A and C in the 1920s by Vallee and Carre in France and by Waldmann in Germany, and the subsequent recognition in the 1940s and 1950s by the Pirbright group of the three Southern African Territory Types SAT 1-3, and Asia 1. 4. The development of in vitro techniques for the growth of the virus which have been crucial for the large-scale production of vaccines and for the accurate assay of virus infectivity. Work by Hecke and the Maitlands in the early 1930s, followed by the crucial demonstration by Frenkel in 1947 that large amounts of the virus could be produced in surviving tongue epithelium, formed the basis for the vaccination programmes initiated in Europe in the 1950s. The subsequent development of cell lines has brought a remarkable degree of sophistication to the study of virus growth. 5. The impact of molecular studies on the structure of the virus and its mode of replication which have led to practical applications such as an in vitro test for vaccine potency, rapid diagnosis methods, and international epidemiological surveys. In addition, they have provided the means to design molecular vaccines.

1. Introduction

The massive outbreaks of foot-and-mouth disease (FMD) in Taiwan in 1997 and more recently in the United Kingdom in 2001 provided stark reminders that, despite all the knowledge we have accumulated during the 100 or so years since Loeffler and Frosch (1897) discovered that the causal agent is a virus, even well organized veterinary and scientific services are hard pressed or even helpless when the virus is on the march. In this chapter I will outline the advances made in our knowledge of the disease and its virus since 1897 but initially I will describe why FMD is important, not only to the immediate farming community but also to world trade and even industries seemingly unconnected with an outbreak.

As long ago as the 16th century the importance of the disease was recognised, if indeed the description by Fracastorius (1546) was that of FMD. Most certainly, towards the end of the 19^th century its devastating effects in Europe, particularly in Germany, led the Government there to invite scientists to study the disease and its cause. Germany was not the only country in mainland Europe with the problem and the disease was also present in the United Kingdom in 1839. In addition, there are reports of the disease in Asia in 1842, South America (1871) and Africa (1892). Clearly there can be no certainty that these occurrences were FMD but the descriptions are sufficiently similar to what is seen today that there is little doubt about their identity.

It is generally regarded that FMD is the most contagious of all diseases of farm animals. Cattle, pigs, sheep and goats are all susceptible. Typically, when an animal becomes infected, most members of the herd or flock will become infected. Clinical signs vary considerably in different species. In domestic cattle, following a short incubation period of two to eight days, the disease is characterized by an initial period of pyrexia, depression and anorexia. The vesicles which develop on the dorsal surface of the tongue, dental pad, lips, buccal mucosa and muzzle vary in size but in severe cases may involve the greater part of the tongue. The lesions normally rupture within 24h, releasing vesicular fluid containing up to 10⁸ infectious units per ml. The epithelium is shed, salivation is profuse, and saliva frequently hangs from the muzzle. Subsequent to or concurrent with the mouth lesions, vesicles appear on the feet, particularly in the clefts or on the coronary bands, causing pain and lameness. Vesicles may also occur on the teats and udder, sometimes leading to bacterial mastitis. Loss of productivity is usually estimated to be about 25%. Although the disease is not usually fatal for adult animals, young animals often die, as found with pigs in Taiwan in 1997. Ironically, with most strains of the virus it is unusual for sheep to show clearly overt signs of the disease, but they proved to be effective transmitters of the disease in the United Kingdom in 2001. The need to stop movement of animals during an outbreak leads to considerable financial losses in the farming community and the size and widespread nature of the U.K. 2001 outbreak led to much greater financial losses to the tourist industry.

The disease also occurs in many wildlife species which makes its control in several countries problematic. Of particular importance in this connection is the susceptibility of the African buffalo in which infection normally occurs in the absence of observable clinical signs. Hedger (1981) is of the opinion that, although many hosts are susceptible under experimental conditions (e.g. by inoculation of the virus or close contact with infected animals), under natural conditions these hosts would not represent a danger to domestic stock. Even the suggestion by Capel-Edwards (1971) that brown rats (Ratus norvegicus), because of their close association with farm animals and their ability to migrate over considerable distances, could play a significant role in the spread of the disease, was discounted by Hugh-Jones in 1970 on the basis of a study of the extensive 1967-69 epizootic in England.

Transmission of the disease is primarily from the infected animal itself, especially during the early febrile stage when virus is present in the organs, tissues and body fluids. Affected animals shed virus in vesicular epithelium and fluid, saliva, milk, faeces, urine, semen and vaginal secretions. Moreover, virus is excreted before the development of clinical signs.

2. Landmarks in the History of the Disease

The landmark papers on the disease were published by Loeffler and Frosch in 1897 when they showed that it was caused by a filterable agent and that serum from convalescent animals “neutralized” it. Clearly influenced by the brilliant pioneering studies of Pasteur and Koch and their colleagues, the primary objective of the work on FMD following the discovery of its aetiology was to develop a vaccine. It is a sobering thought that, despite this recognition, it was not until 1952 that comprehensive vaccination against the disease was first undertaken. The initiation of vaccination of cattle in Holland, France and Germany was an immediate success and it is somewhat bewildering to the author that the policy was stopped in 1991, in his opinion for spurious reasons. I enlarge on these reasons below.

The findings which I regard as the subsequent landmarks in the history of the disease are arranged chronologically in Table 1. Although most are self explanatory, a small section of text summarizing their importance is provided for each landmark. To avoid unnecessary repetition of the more extensive descriptions provided by other authors which appear elsewhere in the book, I have kept these remarks brief.

2.1. Identification of the Causal Agent 1897

This observation was not only important in FMD history but also because it was the first example of an animal disease caused by a virus. All the early work on the disease stemmed from the observation that sera from convalescent animals “neutralized” the agent by protecting them from infection.

2.2. Laboratory Models for the Disease 1920 and 1951

The demonstration that the guinea pig could be infected experimentally was particularly important because the lesions obtained resembled those found in the naturally susceptible hosts, i.e. blisters on the feet and tongue, and loss of condition. Moreover, they provided the means to test experimental vaccines and to produce hyperimmune sera for serological tests. The subsequent discovery by Skinner in 1951 that the suckling mouse could be infected by inoculation provided a cheap laboratory animal which was widely used before the introduction of tissue culture methods, because it is generally as sensitive as cattle for titration of the virus. Even now it is used in some laboratories for vaccine potency assays. It was also used extensively by Skinner in attempts to produce an attenuated vaccine.

2.3. Demonstration of Antigenic Variation 1922-1954

This finding is of crucial importance in studies on the epidemiology of the disease and its control by vaccination. The initial discovery of three serotypes O, A and C in the 1920s was followed by the observation that there was significant variation within these serotypes which led to problems in the major outbreak in Mexico in 1946-1954. The excellent experimental type A vaccine produced from a virus isolate in a 1932 outbreak of the disease in the U.K. was ineffective against the serotype A virus causing the outbreak in Mexico (Galloway et al., 1948). Similarly, the serotype O vaccines being used on a large scale in Western Europe in the 1950s proved ineffective in the face of a serotype O virus which was introduced from South America. These observations were forerunners of the quasispecies theory which has been studied extensively by Domingo et al. (2003) (Chapter 10).

Table 1. Landmarks in the history of foot-and-mouth disease

Year	Achievement
1546	Description of the disease (Fracastorius).
1897	Identification of the causal agent (Loeffler and Frosch); first example of an animal disease caused by a virus.
1920	Demonstration that guinea pigs are susceptible to the disease; the first small experimental animal to be used for FMD work (Waldmann and Pape).
1922-6	Recognition of three distinct serotypes O, A and C, of the virus (Vallee and Carre; Waldmann and Trautwein).
1925	First vaccination against the disease (Vallee et al.)
1927	Recognition of antigenic variation within serotypes (Bedson; Waldmann and Trautwein).
1930	Growth of virus outside animal body (Hecke; Maitland and Maitland).
1931	First estimates of size of virus (Galloway and Elford).
1947	Growth of virus on large scale in tongue tissue fragments, making mass vaccination possible (Frenkel).
1948	Recognition of three serotypes from Southern Africa distinct from O, A and C (Brooksby).
1948	Vaccination of 2 × 10^6 animals in Argentina (Rosenbusch et al.).
1951	Use of suckling mouse as experimental animal (Skinner).
1952	Mass vaccination using in vitro grown virus started in Holland.
1954	Recognition of 7^th serotype, Asia 1 (Brooksby).
1958	Observation of virus in electron microscope (Bachrach and Breese; Bradish et al.).
1958	Role of 146 S particle in immunization (Brown and Crick). Isolation of infectious ribonucleic acid from the virus (Brown et al.).
1959	Isolation of virus from carrier animals (van Bekkum et al.).
1962-4	Growth of virus in a cell line (Mowat and Chapman; Capstick et al.; de Castro).
1963	Purification of the virus particle (Brown and Cartwright; Bachrach et al.).
1965	Demonstration of recombination between virus strains (Pringle).
1966	Viral polymerase recognised by serological methods (Cowan and Graves).
1969	Protein composition of virus determined (Wild et al.; Burroughs et al.).
1969	Importance of single protein in immune response recognised (Wild et al.).
1973	Demonstration that a single isolated protein will evoke neutralizing antibody (Laporte et al.).
1977	Biochemical mapping of the virus genome (Sangar et al.).
1978	Viral RNA polymerase within virus particle (Denoya et al.).
1981	Expression in E. coli cells of the immunogenic protein (Kleid et al.)
1982	Chemical synthesis of a peptide which e...