Vesicular Stomatitis

Agent
Hosts
Epidemiology
Vesicular Stomatitis As a Biological Weapon
Clinical Features
Laboratory Diagnosis
Differential Diagnosis
Treatment
Prevention
Outbreak Control
Public Health Issues
References

Agent

Viral Classification

Vesicular stomatitis (VS) is a viral infection that causes the formation of vesicles around the mouth, lips, coronary band, and teats of affected animals. The clinical signs are similar to those of foot-and-mouth disease (FMD), and the two diseases can easily be confused.

Family: Rhabdoviridae

Organisms from this family are uniquely able to infect a wide range of hosts: mammals, fish, insects, and plants (see References: Aeillo).

Genus: Vesiculovirus

Serotypes: VS virus New Jersey (VSV-NJ) and VS virus Indiana (VSV-IN), which has subtypes 1, 2 (cocal), and 3 (alagoas) (see References: Blickwede)
Other viruses in this genus that can experimentally cause vesicular lesions in domestic animals and in humans: Piry, which was first isolated from an opossum in Brazil; Chandipura, which was isolated from a person in India; and Isfahan, which has been isolated from sandflies and humans in Iran (see References: Rodriguez 2008)

Viral Characteristics

Large, bullet- or rod-shaped virion that is 65 to 185 nm in size
Nonsegmented, negative-strand RNA virus
Gene expression is controlled by distance from the single transcriptional promoter (see References: Flanagan)

Environmental Survival

Effective disinfecting agents (see References: Rodriguez, OIE):

2% sodium carbonate
4% sodium hydroxide
2% iodophore disinfectants
Chlorine dioxide disinfectants
Ether and other organic solvents
1% formalin

Inactivated by temperature of at least 580C for 30 minutes
Stable between pH 4.0 and 10.0
Capable of surviving for long periods of time at low temperatures

Hosts

VSV can affect a variety of livestock species as well as wild animals. It has also been shown to be a zoonotic agent. Predominant animal hosts include (see References: Rodriguez 2008):

Horses
Cattle
Swine
Donkeys
Mules
South American camelids
Sheep and goats (fairly resistant and rarely develop infections)
Deer, raccoons, bobcats, monkeys (have been experimentally infected)

Epidemiology

Transmission

Although transmission occurs via animal-to-animal contact, mechanical vectors, and biological vectors, the relative importance of each of these routes in the spread of the virus among livestock populations remains unclear (see References: Stallknecht).

Direct contact (most common)

Transmucosal or transcutaneous routes
Viral sources (eg, saliva, exudate, epithelium of open vesicles); transmission can occur through eating or coming into contact with substances contaminated with saliva or fluid from the lesions of infected animals (see References: CFIA)

Mechanical vectors

Milking machines
Common feed and water troughs
Feeding equipment
Bedding

Source: APHIS: Information about vesicular stomatitis for the beef producer (see References).

Biological vectors

Small mammals (rodents) have been suspected of serving as vectors, although none have yet been identified (see References: Blickwede).

Arthropod vectors can transmit the disease also (see References: Rodriguez, Mead):

Transovarial transmission has been shown in sand flies (Lutzomyia shannoni) and black flies (Simuliidae)
VSV-NJ has been isolated from several possible vectors:

Biting insects: Culicoides (biting midges), Simuliidae (black flies), Aedes (mosquitoes), Lutzomyia (sand flies)
Nonbiting insects: Chloropidae (eye gnats), Anthomyiidae, Musca (house flies)
Except for Lutzomyia and Simuliidae, the role of these other insects in the transmission is unknown

Competent vectors for VSV-IN (see References: Mead) include:

Aegypt (?)
Aedes (mosquitoes)
Simuliidae (black flies)
Lutzomyia (sand flies)

Variations in temperature, precipitation (including timing), elevation, and vegetation all effect the diversity, density, and activity of the insect vector species (see References: Blickwede).
Because of the role of arthropod transmission in VS, outbreaks in the United States usually stop about 2 weeks after the first killing frost. Other modes of transmission are thought to be responsible in outbreaks that do not stop at that time.

Soil and plants are also suspected as vectors (see References: OIE).

Risk Factors

No geographic factors have been associated with VSV-IN. For VSV-NJ, the following geographic factors have been identified (see References: Mead):

Higher risk for cattle pastured in or near lower mountain, moist forests (500 to 1,500 m above sea level)
Higher risk for pastured animals in tropical dry forests
For cattle pastured in other regions, the highest risk is between sea level and 500 m above sea level

Increased risk with the presence of poultry
Long calving interval (see References: Mead)
Increased risk in areas with the presence of breeding sites for sand flies and black flies (riverways and valleys) (see References: Mead 2000).

Occurrence

The occurrence of VS is currently restricted to North America, Central America, and the northern part of South America.

VSV-NJ is the predominant serotype associated with the more recent epizootics in the Western Hemisphere (1982-1983, 1984-1986, 1995, 1997) (see References: Mead 2000).
VSV-NJ and VSV-IN 1 are found in the United States and Central America.
VSV-NJ and VSV-IN 1, 2, and 3 are found in South America; both are enzootic in Mexico, Colombia, Venezuela, Panama, and Costa Rica.

VS occurs throughout the year in subtropical and tropical areas of the Americas.
During the warm months in the southern and western United States, outbreaks occur irregularly at 10- to 15-year intervals (see References: Rodriguez 2008f).

VSV-NJ is enzootic on Ossabaw Island, Georgia (see References: Mead 2000).
VSV-IN emerged in epizootics in the United States for the first time in 35 years in 1997 and 1998 (see References: Mead 2000).
States involved in epizootics involving both serotypes have included New Mexico, Utah, Arizona, Wyoming, Texas, and Colorado (see References: Blickwede).

Historically, the disease has been found for short periods of time in other areas of the world:

It was first recognized as a disease entity in 1916 when it caused significant problems in Midwest collection centers for horses used in World War I. It then spread to eastern US shipping ports and eventually to France (1915 and 1917 outbreaks), but it died out in Europe (see References: APHIS: Vesicular stomatitis).
It was described in South Africa in 1886 and 1887 but has since been eradicated.
It was described in Canada in 1949. Generally, the virus does not move that far north.

Vesicular Stomatitis As a Biological Weapon

VS is considered a suitable agent for a biological weapon for the following reasons:

It is easily confused with FMD. The economic repercussions of misdiagnosis in an animal population are significant, involving loss of markets for live animals, meat, and animal genetic work).
Substantial direct and indirect economic losses to livestock producers result from an outbreak. For example, the total cost to 13 dairy farmers during the 1982 US outbreak was $95,752, an average of $253 per case (see References: Rodriguez 2008).
The wide range of possible vectors make the disease difficult to eradicate.

Clinical Features

VS is characterized by a high morbidity rate (up to 90% in a herd) but a very low mortality rate.

Clinical Features of Vesicular Stomatitis in Animals*
Feature	Characteristics
Cattle
Incubation period	2-21 days
Clinical signs	Excessive salivation Blanched raised or broken vesicles of various sizes in mouth Lesions on tongue, lips, dental pad, gums, hard palate, and sometimes muzzle and around nostrils Lesions around coronary bands on feet Teat lesions Fever (1040F-1060F) occurs immediately before or at time lesions first appear but is of short duration and is rarely detected Drooling or frothing at mouth
Complications	Decrease in milk production Mastitis due to secondary infections Lesions so painful that animal refuses to eat or drink Severe weight loss Cows with teat lesions: may refuse to nurse, resulting in early weaning Lameness in <5% of cattle Ulcers: may take up to 2 months to heal, and healing animals may still spread disease Broken blisters leave raw, sore areas If infected cows become debilitated, they may experience delayed uterine involution and subsequent delays in resumption of normal estrous cycles after calving Older lactating cows are at higher risk than non-lactating cows or calves
Case-fatality rate	Mortality rate very low Recovery generally in about 2 wk
Horses
Incubation period	2-21 days
Clinical signs	Excessive salivation Blanched raised or broken vesicles of various sizes in mouth Lesions on upper surface of tongue, surface of lips, around nostrils, on gums, and on corners of mouth (see DEFRA figure) Lesions around coronary bands on feet Fever (1040F-1060F) occurs immediately before or at time lesions first appear but is of short duration and is rarely detected Broken blisters leave raw, sore areas Animal may chomp jaws, drool, and rub mouth on manger or other objects
Complications	Lameness Lesions can be so painful that animal refuses to eat or drink
Case-fatality rate	Mortality rate very low Recovery generally in about 2 wk
Swine
Incubation period	2-21 days
Clinical signs	Excessive salivation Blanched raised or broken vesicles of various sizes in mouth and on snout Foot lesions and lameness frequent Fever (1040F-1060F) occurs immediately before or at time lesions first appear but is of short duration and is rarely detected
Complications	Lameness Lesions can be so painful that animal refuses to eat or drink Broken blisters leave raw, sore areas
Case-fatality rate	Mortality rate very low Recovery generally in about 2 wk
Humans
Incubation period	24-48 hr
Clinical signs	Acute influenza-like symptoms (eg, fever, muscle aches, headaches, malaise) Lesions rare but resemble herpes virus when they occur Disease course is 4-7 days
Complications	May go undetected because of missed or incorrect diagnosis
Case-fatality rate	Zero
Adapted from OIE; APHIS: Vesicular stomatitis; CFIA; Rodriguez 2008; Mead (see References).

Characteristics of VS That Distinguish It From FMD

Affects horses
Sporadic incidence in herd
Less severe in young animals
Stabled animals usually not affected
Lesions at more than one site occur in only a small percentage of animals
No rumen lesions observed at necropsy
No heart lesions observed at necropsy
Distinct histologic appearance of lesions on the tongue

Cells in the affected area of stratum spinosum stain more deeply eosinophilic than normal, have a pyknotic nucleus, and are separated by an intercellular edema.
The cells do not become separated as they do in FMD but remain sufficiently attached to each other to form a lace-like or reticular pattern in the stratum spinosum.

Source: Rodriguez 2008 (see References).

Laboratory Diagnosis

Because VS is often clinically indistinguishable from FMD, confirming a diagnosis with laboratory tests is critical. An animal has VS if it demonstrates clinical signs that are consistent with the disease and has a positive viral isolation and/or has one or more positive serologic tests (see References: Blickwede).

Sample Collection

Each of the following should be collected from two or three animals (note that old necrotic or fibrinous material that is difficult to remove is not a good sample):

As much vesicular fluid as possible
Epithelium covering a vesicle or the flaps of epithelium still attached to a broken vesicle (minimum 0.4 g)
Other good specimen sources: oral, nasal, pedal, and mammary lesions (see References: APHIS: Vesicular stomatitis)
About 5 mL of esophageal-pharyngeal fluid from convalescent cattle, sheep, or goats, immediately diluted with an equal volume of cell culture fluid (eg, Hank's balanced salt solutions with lactalbumin hydrolysate) and shaken vigorously for about 1 minute; if solution turns yellow (indicating solution is too acidic and may inactivate the virus), discard it and collect another sample

Specimens can be placed on ice if they can be delivered to lab within 24 hours
Specimens that cannot immediately be sent to a lab should be quick-frozen and not allowed to thaw during transit. When dry ice is used, verify that the vials are tightly sealed with stopper and tape so that no carbon dioxide enters the vial (carbon dioxide can lower the pH and inactivate the virus)
Epithelium can also be placed in buffered glycerin and kept at 390F (40C) or 40F (200C); the epithelium-to-glycerin ratio should not exceed 1:10

Source: APHIS: Vesicular stomatitis (see References).

Identification of the Agent

Virus isolation

Inoculation into embryonated chicken eggs, mice, tissue culture systems (chick fibroblasts, pig kidney, BHK-21, vero), snout of pigs, footpad of guinea pigs, horses, and cattle

Viral antigen detection

Complement fixation test
Enzyme-linked immunosorbent assay (ELISA)
Neutralization tests in tissue culture, embryonated chicken eggs, or suckling mice

Source: OIE (see References).

Serologic Tests

Paired acute and convalescent serum samples need to be collected for these tests (about 5 mL of blood with anticoagulant or 10 mL of serum)
ELISA
Complement fixation
Virus neutralization test (viremia ends about 5 days after disease onset)

Source: OIE; Blickwede; APHIS: Vesicular stomatitis (see References).

Differential Diagnosis

As discussed, VS can be clinically similar to FMD. It can be clinically similar to many other diseases as well (see References: OIE, Rodriguez):

Swine vesicular disease
Vesicular exanthema of swine
Infectious bovine rhinotracheitis
Bovine viral diarrhea
Bluetongue
Foot rot
Chemical and thermal burns
Rinderpest
Malignant catarrhal fever
Contagious ecthyma
Lip and leg ulceration

Treatment

There is no specific treatment for VS, but several treatments can be used for symptoms and to reduce secondary infection (see References: APHIS: vesicular stomatitis):

High-energy liquid gruel feed or electrolytes added to the water supply can be helpful for animals having difficulty eating or drinking.
Oral ulcers can be swabbed with a 1% to 2% solution of Lugol's iodine.
Foot ulcers can be sprayed twice daily with a saturated solution of copper sulfate.
Teat ulcers can be treated with spray solutions of antibiotics and anti-inflammatory drugs.

Prevention

Accept new cattle only from sources that have not had animals with clinical signs of VS in the past 3 months.
Isolate newly arrived cattle and calves offsite and as far away from the main herd as possible for at least 21 days.
Precautions should be taken with herds that have already been infected with VSV because cattle can become reinfected shortly after recovering from a previous infection.
Obtain health certificates for all imported animals.
Wear protective clothing when handling suspect animals.
Disinfect milking machines between cows, and milk infected cows last.
No effective vaccine against VSV exists (see References: Flanagan).

Subunit- or DNA-mediated vaccines for VSV have met with limited success.
Use of live field strains have only been attempted under emergency conditions.
Live attenuated vaccines have not been investigated.
In laboratory experiments, a modified live virus in which the nucleocapsid gene, essential for viral replication, is moved to promoter-distal positions in order to down regulate its expression has been successful.

Source: APHIS: vesicular stomatitis (see References).

Outbreak Control

Laboratory diagnosis must be performed rapidly.
Animal movement should be restricted:

Do not move animals suspected of having VS from the premises until a definitive diagnosis has been made.
Do not move animals from an infected premise, except for slaughter, for 30 days after the last lesion has healed.

All animals with lesions should be isolated from healthy animals, preferably indoors.
Control insects as much as possible:

Treat animals and premises with appropriate insecticides.
Eliminate habitats favorable to insect survival: screen windows of all buildings where animals are housed and eliminate standing water and objects that attract insects.

Isolate dead animals for pickup by a salvage truck; spray the carcasses around the mouth, teats, and feet with disinfectant and treat them with insecticide.
Take precautions to avoid transferring equipment and personnel between isolates and the main herd:

Use separate sets of equipment for each group.
Thoroughly clean and disinfect all shared equipment, feed bunks, and water sources daily.
Instruct personnel to shower and change clothing and boots when moving between isolates and the main herd.
Care for the main herd before the isolated animals.

Public Health Issues

VS is transmissible through aerosolization or direct exposure to humans who come in contact with infected animals. The disease causes influenza-like symptoms in humans (see References: CFIA).

References

Aeillo S, ed. Vesicular stomatitis. In: Merck veterinary manual. Ed 8. Whitehouse Station, NJ: Merck & Co, 1998 [Full text]

APHIS (Animal and Plant Health Inspection Service). Information about vesicular stomatitis for the beef producer. Aug 1996

Blickwede M, Dolz G, Herrero MV, et al. Neutralizing antibodies against Vesicular Stomatitis viruses (serotypes New Jersey and Indiana) in horses in Costa Rica. J Vet Diagn Invest 2002;14(5):438-441 [Abstract]

CFIA (Canadian Food Inspection Agency). Animal Products, Animals Health and Production. Vesicular Stomatitis. Aug 12, 2003 [Web page]

DEFRA (Department for Environment Food and Rural Affairs). Animal health and welfare. Vesicular Stomatitis: pictures. May 24, 2005 [Web page]

Flanagan EB, Aamparo JM, Ball AL, Rodriques LL, Wertz GW. Rearrangement of the genes of Vesicular Stomatitis virus eliminates clinical disease in the natural host: new strategy for vaccine development. J Virol 2001;75(13):6107-6114 [Abstract]

Mead DG, Ramberg FB, Mare CJ. Laboratory vector competence of black flies (Diptera: simuliidae) for the Indiana serotype of Vesicular Stomatitis virus. Ann N Y Acad Sci 2000;916:437-443 [Abstract]

OIE (Office International des Epizooties/World Organization for Animal Health). Vesicular stomatitis. Technical disease cards database. 2002 [Web page]

Rodriguez L. Vesicular stomatitis. In: US Animal Health Association, Committee on Foreign Animal Disease. Foreign animal diseases: the gray book. Ed 7. Part III, chap 47. Richmond, Va: US Animal Health Assoc, 2008:423-30 [Full text]

Stallknecht DE, Perzak DE, Bauer LD, Murphy MD, Howerth E. Contact transmission of vesicular stomatitis virus New Jersey in pigs. Am J Vet Res 2001;62(4):516-520 [Abstract]


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