understood why ruminants but not pigs can become carriers or why some animals develop persistent infection while others do not. Both are areas of ongoing study. Because vaccinated animals can become carriers, the waiting period to prove FMD-freedom is longer when vaccination rather than slaughter is used as an outbreak-control strategy. As a result, many FMD-free countries are resistant to emergency vaccination in case of in outbreak out of concern for the serious trade and economic implications of a prolonged period without FMD-free status. Although the risk of transmission from an individual FMD carrier is considered to be very low, there are many carriers in FMD-endemic regions, possibly increasing the number of chances for carrier transmission to occur. Also, it can be difficult to determine if an asymptomatic infection is neoteric or persistent in the field, as both would be apparently healthy animals that test positive for the FMD virus. This fact complicates disease control, as the two types of subclinical infections have significantly different risks of spreading disease. Cause Of the seven serotypes of this virus, A, C, O, Asia 1, and SAT3 appear to be distinct lineages; SAT 1 and SAT 2 are unresolved clades. The mutation rate of the protein-encoding sequences of strains isolated between 1932 and 2007 has been estimated to be 1.46 × 10−3 substitutions/site/year, a rate similar to that of other RNA viruses. The most recent common ancestor appears to have evolved about 481 years ago (early 16th century). This ancestor then diverged into two clades which have given rise to the extant circulating Euro-Asiatic and South African. SAT 1 diverged first 397 years ago, followed by sequential divergence of serotype SAT 2 (396 years ago), A (147 years ago), O (121 years ago), Asia 1 (89 years ago), C (86 years ago), and SAT 3 (83 years ago). Bayesian skyline plot reveals a population expansion in the early 20th century that is followed by a rapid decline in population size from the late 20th century to the present day. Within each serotype, there was no apparent periodic, geographic, or host species influence on the evolution of global FMD viruses. At least seven genotypes of serotype Asia 1 are known. Transmission The FMD virus can be transmitted in a number of ways, including close-contact, animal-to-animal spread, long-distance aerosol spread and fomites, or inanimate objects, typically fodder and motor vehicles. The clothes and skin of