Rakesh Kumar*, Venketaramireddy Balena and Shailesh Kumar Patel

Division of Pathology1, ICAR-IVRI, Izatnagar, Bareilly – 243 122, India.


Many vesicular diseases are caused by viruses due to their epitheliotropic nature, which are characterized by formation of vesicles. Vesicles are found on oral mucosa, on the feet, and on the mammary glands of females. They lead to more morbidity but less mortality cases but rather lead to production and thereby economic losses to the farmers. Among vesicular disease FMD is one of the extremely contagious, acute viral disease, mainly of all cloven footed domestic animals (Coetzer et al., 1994), and also occur in wild animals characterized by fever, vesicular lesions and erosions of epithelial cells of mouth, tongue, nares, muzzle, feet and mammary glands (Jamal and Belsham, 2013). This disease leads to myocarditis in young animals, thereby early mortality in calves. It is OIE listed “A” disease because of its economic impact and was the first animal virus to be recognized.

Keywords: Vesicular diseases, Foot and Mouth disease, Virus, Livestock, Oral mucosa.


FMD is caused by Aphthovirus grouped under family Picornaviridae which is a small (27-28 nm) non-enveloped ss RNA + senseviruswith icosahedral symmetry (Belsham, 1993).This virus as an etiological agent for FMD was first demonstrated by Loeffler and Frosch in 1897. FMD virus shows 7 Serotypes namely O, A, C, Asia-1, SAT-1, 2 and 3 and with multiple subtypes further in these (Bachrach, 1968).The serotypes A, O, C and Asia 1 are prevalent in India with the order of prevalence as O>Asia1>A~C. These serotypes do not show any cross protection among themselves(Leforban and Sumption, 2010).The serotypes A and O were discovered by Valle and Carre (1922), serotype C by Wailmann and Trautwein (1926) and at last the 7th serotype Asia 1 was discovered in Pakistan from buffaloes in 1954 (Brooksby JB, Rogers, 1957). The incubation period of this virus is 2 to 14 days (OIE, 2012).
Host range
Animals like cattle, buffaloes, sheep, goat, pigs, deer, elephant, llama, alpaca, antelope, hedgehogs, porcupines, kangaroos, guinea- pigs and camels are susceptible. Suckling mice are most susceptible to FMD infection (<14 days old). Horse, donkey, mule, camel are found to be resistant. Many strains show jumping behavior, as many strains infecting the cattle are also seen in deer and wild pigs also (OIE, 2012; Jubb et al., 2007; McGavin and Zachary, 2012; Vegad and Katiyar, 2005).
Economic importance
Mortality is higher in young calves, lambs and piglets around 20% -50% and low in adult animals (1-5%), while in susceptible cloven footed animals morbidity is nearer to 100% that’s why leads to production losses.
Transmission (OIE, 2012; Vegad and Katiyar, 2005)
i. By direct contact between susceptible and infected animals.
ii. Direct contact of susceptible animals with contaminated inanimate objects like clothing, foot wears and vehicles etc.
iii. Intake of infected milk.
iv. Inhalation of infectious aerosols contaminated with virus.
v. As FMD virus can be transmitted through airborne route, can spread to long distances. Pigs are most important source for this spread. (Sellers and Parker, 1969; Donaldson and Ferris, 1980; Alexandersen et al., 2002a). This virus can spread up to 300 kilometer through air (Gloster et al., 1981, 1982; Donaldson et al., 1982a, b; Sorensen et al., 2000, 2001).
vi. Virus can come through infected saliva, faeces and urine to the environment and can infect the susceptible population.
vii. There is rare evidence that carrier animals can be the source of infection. This virus usually localizes in oropharynx and persists for 6 months. So, usually the carrier state can remain for 6 months to 3 years in cattle and it is of shorter duration in sheep, goats (6 months) and buffaloes. While pigs do not act as carriers (Hedger and Stubbins, 1971; Alexandersen et al., 2002b).
Higher concentration of virus can be observed in other tissues without the presence of any visible lesions (Burrows et al., 1981; Zhang & Alexandersen, 2004; Arzt et al., 2011).
Clinical signs and gross lesions
The severity of clinical signs depends upon stain of virus, species of the animal, age, breed and individual immune response of the animals. The mortality rate in this disease is less (up to 5%) but high in young calves, piglets and lambs (up to 50%), While, the morbidity can reach up to 100%. Large amount of virus is seen in vesicular fluid but less evidence of virus in faeces (Hyslop, 1965; Scott et al., 1966; Parker, 1971; Garland, 1974).
High fever (104p -106p F), sudden fall in milk yield, stomatitis which leads to anorexia and long ropy strings of saliva hanging with smacking of lips and tongue which is quite characteristic of this disease (Vegad and Katiyar, 2005).Vesicles on buccal mucosa, dental pad and tongue, when these rupture leads to painful mastication in animals. Vesicles are also seen in feet, mainly in the clefts and coronet which leads to lameness. Vesicle on mammary gland, vulva can lead to mastitis and metritis respectively (OIE, 2012; Jubb et al., 2007).Vesicular lesions can extend up to rumen, reticulum, omasum and abomasum. These diseases can lead to abortion in pregnant animals. In calves no vesicular lesions are seen rather extra epithelial lesions are seen in heart i.e. Tigroid heart (necrotizing myocarditis) and acute gastroenteritis which are more dangerous and lead to acute mortality (OIE, 2012; McGavin and Zachary, 2012).This virus can lead to endocrine damage in recovered animals so led to rough coat with long hairs and thereby thermoregulation is affected. These animals with affected thermoregulation are called as panters. Animals mostly show recovery within 2 weeks after infection (OIE, 2012; Vegad and Katiyar, 2005).The presence of vesicular lesions on epithelial surfaces can later on lead to secondary bacterial infection and can cause more general complications.
Sheep and goats
Sheep and goats can show pyrexia, oral lesions and lameness but of milder degree. Agalactia is one of the important feature seen in sheep and goats. But in sheep and goats clinical signs are milder and are not much evident as compared to other animals (Donaldson and Sellers, 2000; Alexandersen et al., 2002c; Hughes et al., 2002).
Fever, hoof lesions on coronary band and inter-digital space are more painful and severe than any other species leads to lameness, oral lesions are not common but snout vesicles are seen. The piglets show frequent mortality (Jubb et al., 2007; McGavin and Zachary, 2012).
Microscopic lesions
The epithelial cells become swollen, rounded and loosen shows pyknotic changes in nuclei and acidophilic cytoplasm. The inflammatory exudate get collected between loosen cells. These cells undergo liquifactive changes later on. In some places cells may be denude. The vesicular fluid contains degenerated epithelial cells, erythrocytes and leucocytes (Vegad and Katiyar, 2005; OIE, 2012; McGavin and Zachary, 2012).
(OIE, 2012; Vegad and Katiyar, 2005)
I. On the basis of history and clinical signs
II. Serological tests: CFT, AGPT, FAT
III. Sandwich ELISA or typing ELISA, RIA, Micro-SNT
IV. Molecular tests: RT-PCR,
V. Nucleic acid hybridization
VI. Nucleic acid sequencing
VII. In-situ hybridization
ELISA is capable to detect viral antigen and its serotypes that’s why often preferred over CFT. For virus isolation calf thyroid cells and BHK-21 cell line are used. Virus neutralization test or ELISA are main prescribed tests according to OIE while CFT is used as an alternate test for viral identification (OIE, 2012; Vegad and Katiyar, 2005).
Differential Diagnosis (OIE, 2012)
Vesicular stomatitis, swine vesicular disease and vesicular exanthema of swine are very difficult to distinguish from FMD clinically. So, it is very important to differentiate these diseases from FMD.
Vesicular stomatitis
It is a vesicular disease caused by Vesiculovirus member of family Rhabdoviridae having two serotypes namely, New Jersey and Indiana. It is mainly an acute disease of horse but also have importance in cattle and pigs which is transmitted by vectors Sandflies, Blackflies, Seasonal outbreaks, direct contact with infected animals and contaminated objects. This virus leads to formation of vesicles on mouth, feet, snout and udder. Resemble FMD and not seen in sheep’s and goats.
Incubation period of this virus is 3 to 5 days. This virus leads to fever and vesicles formation that resemble FMD lesions. Vesicles rupture to cause profuse salivation and anorexia but recovery may occur within 3-4 days. Most severe signs are seen in Horses, with oral lesions, drooling, champing, mouth rubbing, lameness, and coronary band lesions. In Cattle and pigs vesicular lesions in oral cavity, mammary gland, coronary band, and inter-digital region are seen. Which leads to salivation, lameness and recover within 2 weeks. Gross and histopathological lesions are just similar to FMD.
Swine vesicular disease virus/Porcine enterovirus infection (OIE, 2012)
It is a contagious disease of pigs characterized by fever, vesicular lesions and is caused by Enterovirus member of family Picornaviridae. This disease is transmitted by direct or indirect contact with infected animals or feces and contaminated environment, ingestion of contaminated pork, virus excreted from nasal or mouth secretions. It is mainly a disease of pigs with high morbidity but can lead up to 10% mortality in piglets. This disease also resemble with FMD but less severe than FMD. Post-infection protective antibodies are produced in this infection. This virus leads to fever (104p -105p F), vesicles and erosions on snout, mammary glands, coronary band, and inter-digital areas. Vesicles on the coronary band of the claws especially at the heel are almost characteristic which leads to lameness.
Vesicular exanthema of swine (OIE, 2012)
It is an acute, febrile contagious viral disease of swine characterized by formation of vesicles on the snout, around the mouth and on the feet. It is very difficult to distinguish this disease clinically from foot and mouth disease, vesicular stomatitis and swine vesicular disease.This disease is caused by Calicivirus.Although it is a mild disease with low mortality rate but in affected pigs, heavy weight loss can occur. Leads to abortion in pregnant sows and lactating sow become dry.
This disease is often transmitted by direct contact, oro-nasal and lachrymal secretions, urine, faeces, insemination, blood transfer feeding of raw or insufficiently cooked meat. Vesicular lesions occur on the snout, around the mouth and on the feet, accompanied by fever, variable anorexia and malaise. Vesicles can also be seen on the udder and teats of nursing sows. A vesicle on rupture leads to erosive areas. Morbidity is around 100% with no significant mortality.
FMD v/s other similar diseases
i. Rinderpest: It is systemic disease with high mortality, severe leucopenia, necrotic and ulcerative stomatitis, and absence of vesicles, only small greyish-white punctate present, and diarrhea.
ii. MCF: Shows necrotic stomatitis, kerato-conjunctivitis, head and eye form, lesions most prominent on muzzle.
iii. Bluetongue: Foot lesions (coronitis and laminitis) without vesicles.
iv. BVD: Severe diarrhea, erosive oral lesions and high mortality.
v. Foot rot: Foot lesions present causing lameness but vesicles absent.
Prevention and control (OIE, 2012)
i. Provide sanitary conditions to the animals.
ii. Quarantine measures are to be followed.
iii. Slaughter and stamping out policy is taken care of if necessary.
iv. The free movement of animals in herd should not be allowed.
v. The carcass, beddings and infected materials should be disposed of very cautiously.
vi. This virus can be inactivated at temperature more than 50 OC and at a pH 9. Many chemical disinfectants like sodium hydroxide (2%), sodium carbonate (0.2%) and sodium hypochlorite (3%) are quite effective.
vii. Since 2003 onwards, Project Directorate on FMD, ICAR and Government of India harmonized the strains used for vaccine production in India. The serotypes O (Vaccine strain O IND R2/75), A (Vaccine strain A IND 40/00) and Asia 1 (Vaccine strain IND 63/72) were used for vaccine. The serotype C strain was discontinued since October 2003.


FMD is one of the most contagious animal disease which leads to huge economic losses. FMD virus is having wide host range, can spread by different means and having many serotypes (7). All these factors often increasing the chances of mutation in this virus and can lead to development of new variants. Nowadays, the zoonotic significance of this disease is also posing a threat to public. So, it is foremost step to eradicate or control this disease very critically and cautiously.


1. Alexandersen S, Brotherhood I and Donaldson AI. Natural aerosol transmission of foot-andmouth disease virus to pigs: minimal infectious dose for strain O1 Lausanne. Epidemiology and Infection, 2002a; 128:301–312.
2. Alexandersen S, Zhang Z and Donaldson AI. Aspects of the persistence of foot-and-mouth disease virus in animals—the carrier problem. Microbes and Infection, 2002b; 4: 1099–1110.
3. Alexandersen S, Zhang Z, Donaldson AI and Garland AJM. The Pathogenesis and Diagnosis of Foot-and-Mouth Disease J. Comp. Path 2003; 129:1–36
4. Alexandersen S, Zhang Z, Reid SM, Hutchings GH and Donaldson AI. Quantities of infectious virus and viral RNA recovered from sheep and cattle experimentally infected with foot-and-mouth disease virus O UK 2001. Journal of General Virology, 2002c; 83:1915–1923.
5. Arzt J, Juleff N, Zhang Z and Rodriguez L L. The Pathogenesis of Foot and Mouth Disease I: Viral Pathways in Cattle. Transboundary and emerging diseases, 2011; 58(4), 291-304.
6. Bachrach HL. Foot-and-mouth disease. Annu. Rev. Microbiol. 1968; 22:201–244.
7. Belsham GJ. Distinctive features of foot-andmouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure. Progress in Biophysics and Molecular Biology, 1993; 60: 241–260.
8. Brooksby JB and Rogers J. Methods used in typing the virus of foot-and-mouth disease at Pirbright, 1950–55. Methods of typing and cultivation of foot-and-mouth disease virus, European Productivity Agency of the Organisation for European Economic Co-operation, Project, 1957; 208:31-34.
9. Burrows, R., Mann, J. A., Garland, A. J. M., Greig, A., & Goodridge, D. The pathogenesis of natural and simulated natural foot-and-mouth disease infection in cattle. Journal of Comparative Pathology, 1981; 91(4), 599-609.
10. Coetzer JAW, Thomson GR and Tustin RC. Infectious diseases of livestock with special reference to Southern Africa: Volume 1. Oxford University Press Southern Africa 1994.
11. Cottral GE. Diagnosis of bovine vesicular diseases. J am vet. meassoc. 1972; 161(11): 1293-8.
12. Donaldson AI and Ferris P. Sites of release of airborne foot-and-mouth disease virus from infected pigs. Research in Veterinary Science, 1980; 29:315–319.
13. Donaldson AI and Sellers RF. Foot-andmouth disease. In: Diseases of Sheep, 3rd Edn, Martin WB and Aitken ID (Eds) Blackwell Science, Oxford, 2000; pp. 254–258.
14. Donaldson AI, Ferris NP and Gloster J. Air sampling of pigs infected with foot-and-mouth disease virus: comparison of Litton and cyclone samplers. Research in Veterinary Science, 1982a; 33:384–385.
15. Donaldson AI, Gloster J, Harvey LD and Deans DH. Use of prediction models to forecast and analyse airborne spread during the foot-andmouth disease outbreaks in Brittany, Jersey and the Isle of Wight in 1981. Veterinary Record, 1982b; 110:53–57.
16. Foot and Mouth Disease. OIE Terrestrial Manual 2012, Chapter 2.1.5:1
17. Garland A J. The inhibitory activity of secretions in cattle against FMDV. PhD Thesis, University of London 1974.
18. Gloster J, Blackall J, Sellers RF and Donaldson AI. Forecasting the spread of foot-and-mouth disease. Veterinary Record, 1981; 108:370–374.
19. Gloster J, Sellers RF and Donaldson AI. Long distance transport of foot-and-mouth disease virus over the sea. Veterinary Record, 1982; 110:47–52.
20. Hedger RS and Stubbins AG J. The carrier state in FMD and the probang test. State Veterinary Journal, 1971; 26:45–50.
21. Hughes GJ, Mioulet V, Kitching RP, Woolhouse ME, Alexandersen S. and Donaldson A I. Foot-and-mouth disease virus infection of sheep: implications for diagnosis and control. Veterinary Record, 2002; 150:724–727.
22. Hyslop NS. Secretion of foot-and-mouth disease virus and antibody in the saliva of infected and immunized cattle. Journal of Comparative Pathology, 1965; 75:111–117.
23. Jamal SM and Belsham GJ. Foot-and-mouth disease: past, present and future. Vet Res. 2013; 44(1):116.
24. Jubb KVF, Kennedy PC and Palmer N. Pathology of Domestic Animals. Academic Press, New York and London (5th ed.). Elsevier Saunders 2007.
25. Leforban Y and Sumption K. – Foot and mouth disease. In Infectious and parasitic diseases of livestock, Vol. I (P. Lefèvre, J. Blancou, R. Chermette & G. Uilenber, eds). Lavoisier, Paris, 2010; 299–324.
26. Loeffler F and Frosch P: SummarischerBerichtueber der Ergebnisse der UntersuchungenzurErforschung der Maul- und Klauenseuche. ZentBl. Bakt. Parasitkde 1897; 22:257–259.
27. McGavin D and Zachary JF. Pathological basis of veterinary diseases. 4th ed. Mosby, Philadelphia 2007.
28. Parker J. Presence and inactivation of foot-andmouth disease virus in animal faeces. Veterinary Record, 1971; 88:659–662.
29. Sastry GA and Rao PR (2001). Veterinary Pathology 7th Ed. CBS Publisher and Distributors, 485, Delhi-32.
30. Scott FW, Cottral GE and Gailiunas P. Persistence of foot-and-mouth disease virus in external lesions and saliva of experimentally infected cattle. American Journal of Veterinary Research, 1966; 27:1531–1536.
31. Sellers RF and Parker J. Airborne excretion of foot-and-mouth disease virus. Journal of Hygiene, 1969; 67:671–677.
32. Sorensen JH, Jensen CO, Mikkelsen T, Mackay DK and Donaldson AI. Modelling the atmospheric dispersion of foot-and-mouth disease virus for emergency preparedness. Physics Chemistry Earth, 2001; 26:93–97.
33. Sorensen JH, Mackay DK, Jensen CO and Donaldson AI. An integrated model to predict the atmospheric spread of foot-and-mouth disease virus. Epidemiology and Infection, 2000; 124: 577–590
34. Vallée H and Carré H. Sur la pluralité du virus aphteux. CR Acad. Sci. Paris, 1922; 174:1498-1500.
35. Vegad JL, Katiyar AK (2005). A Textbook of Veterinary Special Pathology
36. Waldmann O and Trautwein K. Experimentalleuntersuchungenueber die pluralitet des maul-und klauenseuche virus. Berlin TierarztlWochenschr, 1926; 42:569–571.
37. Zhang Z and Alexandersen, S. Quantitative analysis of foot-and-mouth disease virus RNA loads in bovine tissues: implications for the site of viral persistence. Journal of General Virology, 2004; 85(9):2567-2575.