Foot-and-mouth disease

Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cloven footed animals most notably cattle, pig and sheep. It is well known for its economic consequences due to restriction on the trade in animals and animal products from countries harboring it. Though rarely fatal in adult animals, it ranks first in the Office International des Epizooties (OIE) diseases  owing to nearly cent percent morbidity, rapid spread, severe decrease in livestock production, calf mortality and trade restrictions on animals and livestock products from FMD positive countries. There is upto 25% loss of livestock productivity due to reduced growth rate, decreased milk production and crippled agricultural draught power in developing countries like India. Furthermore, prolonged convalescence, short term immunity with no cross protection between different serotypes of the virus and carrier status complicates the control and eradication of this devastating disease. The disease is characterized by fever, formation of vesicles and blisters in the mouth, udder, teats and on the skin of the inter-digital space in hooves of cloven footed animals. Imported and crossbred cattle suffer resulting in high morbidity, but low mortality. Buffaloes, sheep and goats are also susceptible to the disease. The disease spreads by direct contact or indirectly through infected water, manure, hay and pastures, and by the cattle attendants. It is known to spread through recovered animals, field rats, porcupines and birds. The air-borne transmission of the virus has also been established.

Epidemiology: FMD virus (FMDV), a member of the genus Apthovirus of the family Picornaviridae, is a single stranded positive sense virus with a RNA genome of ~8.5 Kb. The characteristic feature of FMDV, like other RNA viruses, is its diversity, which has been reflected by the presence of seven distinct serotypes O, A, C, Asia 1 and  South African Territories 1 (SAT 1), SAT 2 and SAT 3 with  multiple subtypes and topotypes within each serotype. The virus population replicates as a pool of related but non-identical genomes, termed viral quasispecies. Besides this, homologous recombination also plays an important role in the diversity of the virus. Recovery from infection with one type does not render the animal immune from infection with other type of the virus. Hence, repeated infection with foot and mouth disease can take place in the same animal or herd. FMDV is endemic in India and in recent years FMDV types O, A and Asia 1 have been encountered throughout the year. In terms of number of outbreaks caused, serotype O predominates in India followed by serotypes A and Asia 1 in that order. However, existence of serotype C has not been reported since 1995. Studies relating to antigenic and genetic characteristics of FMDV have indicated that type A virus is the most diverse serotype. it is common in Africa, Asia, Europe, South America, Japan and Philippines. USA is not having FMD since 1929. Australia and New Zealand have never had FMD.

Symptoms: The virus gains entry into the blood stream of animals through injury to the lining membrane of the mouth, tongue, intestines, clefts of hooves and other similar parts. The incubation period in natural infection is 2 to 5 days. In artificial infection, the temperature rises to 40oC to 40.5oC in 24 and 48 hr. On account of the presence of blisters in the mouth, the animal does not eat well and makes a characteristic smacking sound with profuse salivation. The animal looses appetite and body weight, the milk production is considerably reduced or stops completely. Vesicles may also develop in the interdigital skin and coronary band of the feet. It goes lame on account of the painful foot lesions. The virus also attacks internal organs such as stomach, heart and endocrine glands. Recovery from the disease takes place in about 3 weeks, but it is followed by a number of complications, viz. invasion by pus-forming bacteria, maggot formation and shedding of the hoof which may result in permanent deformity of the part and in lameness. Animals that have recovered from the disease are characterized by a dry and rough coat, with long hair. The animal cannot be put to hard work, especially in the sun and it gasps for breath, a condition known as 'panting' which is more severe in the crossbreds than in the indigenous breeds of cattle. If the wound exists for prolonged period of time, overgrowing of the hoof can occur. Pregnant animals can abort.

Diagnosis: Quick spread and the occurrence of lesions in the mouth and feet of affected animals are quite characteristic. The disease presents some similarity to rinderpest, from which it can be readily differentiated by the absence of diarrhoea and by the presence of foot lesions. Confirmation of the diagnosis is done by using the affected tongue epithelium or material from the foot lesions. Isolation of the virus, when necessary, is attempted by inoculating the suspected material into foot-pads of guinea-pigs, unweaned mice, cell culture or in cattle.

Demonstration of specific virus antigen in vesicular fluid or epithelial tissue suspension is used for the identification of the virus type. The virus propagated in suitable cell-culture system can also be used for demonstration of the type specific antigen. Besides the conventional tests, like micro-complement fixation and micro- neutralization, the micro ELISA and its various modifications are routinely used for the diagnosis of the disease. Molecular techniques viz. nucleic acid hybridization with specific probes, antigen capture PCR and nucleotide sequencing have been used for precise diagnosis and for strain differentiation. In sero-epidemiological surveys, tests for demonstration of type-specific neutralizing antibodies and group specific virus infection associated (VIA) antigen are often used. Quantitative tests for assay of antibodies using c-ELISA with polyclonal and monoclonal antibodies have been standardized and applied for seromonitoring purposes.

Differential diagnosis: The diseases to be differentiated include vesicular stomatitis, Vesicular exanthema, bluetounge, bovine viral diarrhoea and rinderpest. The details of animal inoculation tests for differential diagnosis are as given here.

Treatment: No therapeutic agent has been found till now to cure foot-and-mouth disease. The use of drugs by field workers is resorted to only as a measure of aiding in the natural process of recovery. Thus, the external application of antiseptics contributes to the healing of the ulcers and to ward off the attacks by flies.

Prevention and control: Prevention is the only dependable method of dealing with foot-and-mouth disease. In countries where the disease does not exist or where the incidence is very low, legislative action has made low rate of incidence of all suspected cases of the foot-and-mouth disease. The usual measures adopted in these countries are slaughtering of all affected and in-contact animals, a thorough disinfection of all utensils and clothes of attendants and a strict watch over animals in the neighboring areas. The slaughtered animals are buried at least 4-5 m deep in the ground and covered with lime and earth. The affected premises are not used for at least 30 days and are tested for infectivity at the end of this period by allowing small groups of animals into them.

The adoption of a policy of slaughter involving cattle is impracticable in countries like India. Besides, hygienic measures, the method of control employed in this country rests with selective vaccination. The vaccines used in India are all killed vaccines. Quadrivalent BHK-21 cell cultured, formaline or BEI inactivated, aluminium- hydroxide gel absorbed or oil adjuvanted foot-and-mouth disease virus vaccines have been developed and produced in India. These have proved to be very effective in controlling the disease when carried out systematically. Research is also being done in recent years to improve upon the vaccine, particularly to reduce the dose and cost and to incorporate suitable virus strains. Facilities have also been established for the application of bio-technological innovations like DNA recombinant technology for possible improvement of diagnostics and vaccines. Use of better inactivating agents, adjuvant and quality assurance are other aspects of research undertaken on this vaccine.

On account of the 3 types of viruses (O, A and Asia-1) causing it, FMD is encountered periodically. It is, therefore, necessary to carry out vaccination with a polyvalent vaccine regularly. Heavy milch animals and exotic breeds of cattle bred for milk should be protected regularly. It is advisable to carry out 2 vaccinations at an interval of 4 - 6 months. Concentrated oil adjuvant vaccines with BEI inactivation of virus and 3 ml dose are in use in India. There may be a swelling at the site of inoculation, which may persist for some time and disappear later without any discomfort to the animal.