Foot-and-mouth disease: past, present and future

Abstract

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous economic losses when incursions occur into countries which are normally disease free. In addition, it has long-term effects within countries where the disease is endemic due to reduced animal productivity and the restrictions on international trade in animal products. The disease is caused by infection with foot-and-mouth disease virus (FMDV), a picornavirus. Seven different serotypes (and numerous variants) of FMDV have been identified. Some serotypes have a restricted geographical distribution, e.g. Asia-1, whereas others, notably serotype O, occur in many different regions. There is no cross-protection between serotypes and sometimes protection conferred by vaccines even of the same serotype can be limited. Thus it is important to characterize the viruses that are circulating if vaccination is being used for disease control. This review describes current methods for the detection and characterization of FMDVs. Sequence information is increasingly being used for identifying the source of outbreaks. In addition such information can be used to understand antigenic change within virus strains. The challenges and opportunities for improving the control of the disease within endemic settings, with a focus on Eurasia, are discussed, including the role of the FAO/EuFMD/OIE Progressive Control Pathway. Better control of the disease in endemic areas reduces the risk of incursions into disease-free regions.

Figure 1

Genome organization of FMDV and the structure of virus. The FMDV genome includes a single large ORF, indicated by the shaded rectangle. The regions within the rectangle indicate the individual proteins. The 5’ UTR includes several distinct structural elements including: a poly(C) tract (Cn), 3 or 4 pseudoknots (PK) and the internal ribosome entry site (IRES). The VPg peptide is made in 3 different forms (encoded by the 3B_1-3) and each acts as the primer for RNA synthesis so each RNA genome, when synthesized, is covalently linked to a VPg. The assembly of virus particles from protomeric and pentameric subunits is indicated. Assembled virus particles contain a single copy of the viral RNA and 60 copies of the 4 different capsid proteins (VP1-VP4). Self-assembly of empty capsid particles, lacking the RNA genome, can also occur. The VP4 protein is internal.

Figure 2

Geographical distribution of seven pools of foot-and mouth disease viruses. Serotype O FMDV is the most widely distributed serotype of the virus (in 6 of the 7 indicated virus pools) whereas, in contrast, SAT3 is only present in pool 6 (within southern Africa). The Asia-1, SAT1 and SAT2 serotypes also have quite limited geographical distribution. However, individual countries can have multiple serotypes in circulation at the same time and hence it is necessary to be able to determine which serotype is responsible for an outbreak if vaccination is to be used. Countries which are normally free of the disease (marked in yellow) can still suffer incursions of the virus which can have high economic costs.

Figure 3

The FAO/EuFMD/OIE Progressive Control Pathway for FMD. The status of countries on the PCP-FMD is evaluated according to defined criteria. Countries with endemic disease are in stages 0 to 3 while countries with no endemic disease within livestock are at stage 4 or above. The image was kindly supplied by EuFMD.