Bluetongue Disease

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

Agent

Bluetongue is a noncontagious, arthropod-borne viral disease of domestic and wild ruminants (see References: Murphy 1999; OIE: Manual of standards 1991). Bluetongue virus (BTV) has the following characteristics:

• Family: Reoviridae, genus Orbiviridae
• 24 serotypes, four (10,11, 13, 17) of which are active in the United States (see References: MacLachlan 1997, Stott 1998)
• Serotype 2 was briefly reported in Florida
• Nonenveloped; genome is 10 pieces of fragmented, double-stranded RNA
• VP7 is the highly conserved protein for identification and is located on the outer protein layer; VPs is the variable protein used for identifying serotype
• Susceptible to disinfection by iodophores or phenols; betapropiolactone or pH outside the range of 6 to 8 (acetic acid) can also inactivate it; resistant to lipid solvents such as ether (see References: OIE: Technical card database)
• Highly stable in refrigerated blood or other protein sources

Hosts

• All ruminants are susceptible.
• Sheep are the main hosts and exhibit the most clinical disease.
• Infected cattle, goats, camels, buffaloes, and wild ruminants typically have subclinical disease.
• Cattle are considered amplifiers and maintenance hosts.

Source: Aiello 1998 (see References).

Epidemiology

Transmission

Biological

• The biological vectors of BTV are Culicoides midges (see figure [from References: DEFRA: Bluetongue: pictures]). Types include but are not limited to:
• C variipennis sonorensis has an oral susceptibility rate of 19.5% (major vector.) (see References: Fu 1999)
• C imcola
• C brevitari
• The peak season for infection is midsummer to early fall.
• The vectors breed in moist soil and avoid the interior of buildings.
• For transmission to occur, vectors must feed on animals while they are viremic and climatic conditions must be suitable for the virus to complete development within the vector (see References: DEFRA: Bluetongue disease control strategy).
• OIE standards indicate the period of infectivity to be 100 days.
• Adult cattle are viremic (able to pass virus to vector) for less than 9 weeks after infection (see References: Singer 2001).
• Adult sheep are viremic for less than 50 days.
• In the field, animals are able to pass the virus to the vector for only limited periods.
• Vectors can be transported up to 100 km on the wind (see References: DEFRA: Technical report)

Mechanical

• BTV can be mechanically vectored by means of instruments (blood transfer) during periods of viremia.

In Utero

• BTV can be transmitted in utero (see References: Stott 1998)
• Transmissibility depends on the stage of development, viral strain, and immune status of the dam.
• Sheep are most often affected in the first trimester.
• Cattle are most susceptible between 60 and 140 days' gestation, with a transmission rate of 15% to 20%.

Semen

• Semen containing red or white blood cells can also transfer the virus (low epidemiologic importance). Semen can be infected only when the bull is viremic.

Additional sources: OIE: Manual of standards, Aeillo 1998 (see References).

Occurrence

• Clinical disease occurs in Africa, the Middle East, the Indian subcontinent, southern and western United States, China, Mexico, and the Mediterranean Basin.
• Animals in the Mediterranean Basin have been affected since 1999 (see References: FAO).
• France, Croatia, Yugoslavia, and Kosovo reported outbreaks in 2001.
• Mostly subclinical disease occurs in Southeast Asia, Papua New Guinea, northern South America, and Australia.
• BTV has been detected in northern and eastern Australia.
• Argentina and Brazil reported bluetongue incursions in 2001.
• Canada is reported as BTV-free by national serologic surveys of cattle. Sentinel cattle programs are in place in the Okanagan Valley area where the only historic outbreaks of bluetongue disease have occurred. (see References: Kahrs 1998, USAHA 2002).
• A country can be BTV-free if it meets the requirements set forth by OIE article 2.1.9.2. (see References: OIE: Manual of standards)
• Bluetongue has to be a notifiable disease in the country.
• The country has to be north of 40°N or south of 30°S latitude and not bordered by a non-free zone.
• The country has to have a surveillance program (with 95% sensitivity to detect a 2% infection rate) that demonstrates no BTV in the country after no vaccination within the previous 2 years.
• There must be no evidence of Culicoides in the country by surveillance and monitoring programs.

• There are also allocations for countries or parts of countries to be seasonally disease-free if they have evidence of no transmission or no Culicoides activity.

Additional sources: OIE: Disease information in the last 18 months (see References).

Communicability

• BTV is present in countries between 40°N and 35°S latitude where the Culicoides midge is present (see References: OIE: Manual of standards).
• Locations where the vector is present year-round can have a continuous host-vector cycle (see References: Stott 1998).
• It is not completely understood how the virus reappears in areas with winter but a variety of mechanisms have been proposed (see References: DEFRA: Technical card database):
• Reintroduction in the spring of infected animals or midges
• Prolonged viremia in certain animals
• Persistence in gamma delta T cells of sheep
• Late-term in utero transmission, with birth of a viremic animal at the end of winter
• Over-wintering of infected midges

Bluetongue As a Bioweapon

Bluetongue is considered as a potential bioweapon because of the following factors:

• There is a risk of bluetongue to any country with competent vectors.
• Historically, BTV has produced devastating ovine epizootics and been difficult to eliminate and control in bovine populations.
• Viremic animals cannot be distinguished from nontransmitting animals.
• Widespread infection would result in significant economic costs from lost trade of germ plasm and animal products and regulatory costs would increase.

Source: USAHA (see References).

Clinical Features

The clinical signs are described in the following table. The effects of the disease are related to damage to endothelial cells and systemic vasculitis.

Clinical Features of Bluetongue Disease
Feature	Characteristics
ACUTE FORM*
Incubation period†	7-10 days
Clinical signs	—Pyrexia of  41.6-41.7°C (106-107°F) for 4-12 days —Edema of face, lips, muzzle, and ears —Cyanosis of tongue (bluetongue) —Swelling of oral and nasal mucosa leading to panting and drooling (see Gray Book figure [References: Stott 1998]) —Ulcers in the buccal area, dental pad, and tongue with 3 days progressing to severe necrotic lesions by day 7 —Laminitis manifesed as sheep standing with arched backs, hyperemic coronary bands and, in severe cases, sloughing of the hoof horn (see Gray Book figure [References: Stott 1998]) —Fetal death leading to abortion or reabsorption or birth of depressed lambs in ewes affected in first trimester
Complications	—Loss of part or all of wool 3-4 wek after fever in severely affected sheep —Pneumonia —Sterility
Morbidity and mortality‡	—Morbidity rates: up to 100% —Mortality rates: between 0% and 50%, with most death from inability to eat, weakness from muscle wasting, and inability to ambulate —US strains have lower mortality rates (<30%) than African strains
INAPPARENT FORM§
Incubation Period†	7-10 days
Clinical Signs	—Often no overt clinical signs, just changes in white blood cell counts, fluctuating pyrexia, ad mild eosinophilic dermatitis —Animals with previous exposure may be sensitized (IgE mediated response) (see References: Odeon) and exhibit clinical signs 10 days after re-exposure for 10-20 days —Signs include matted crusty hair, hyperemia to ulceration of oral mucosa, and hyperesthesia. Teats can have exudative dermatitis —Laminitis
Complications	—Cattle often develop hoof rot after the disease due to cracks in the horn —Pneumonia
Morbidity	Usually less than 5%, most effect is from severe production loss
DISEASE IN DOGS**	Pregnant dogs will abort or give birth to stillborn pups and die with in a week. (see References: Wilbur)
*Seen most often in sheep and some types of deer. †Incubation period depends on infective dose, host susceptibility, and viral strain; can range from 5-20 days with 7-10 typical. ‡White-tailed deer and pronghorn antelope have up to 100% morbidity and 80%-90% mortality rates. §Occurs in cattle, goats, and North American elk. **Accidental contamination of canine vaccine that lead to infection occurred in the US in the 1990s (see References: Wilbur 1994), and large African carnivores have shown seroconversion to bluetongue (see References: Aeillo 1998).

Sources: Stott 1998, Aeillo 1998, OIE: Manual of standards (see References).

Differential Diagnosis

Conditions that should be considered in differential diagnosis include:

• Contagious ecthyma (agent: parapox virus)
• Foot-and-mouth disease (agent: foot-and-mouth disease virus of the genus Aphthovirus, family Picornaviridae)
• Infectious bovine rhinotrachei (agent: bovine herpes virus-1)
• Bovine viral diarrhea (agents: bovine viral diarrhea virus, pestivirus)
• Malignant cattarhal fever (agents: ovine herpesvirus-2 and alecelaphine herpesvirus-1)
• Photosensitization
• Parainfluenza 3 viral pnuemonia (agent: parainfluenza 3 virus)
• Polarthritis/footrot/foot abscess (multiple agents and causes including Fusobacterium necrophorum)
• Plant poisonings (agents: Quercus and others)
• Peste des petits ruminants (agent: peste des petits ruminants virus, family Paramyxoviridae)
• Coenurosis (agent: Taenia multiceps)
• Epizootic hemorrhagic disease (agent: epizootic hemorrhagic disease virus [EHDV])

Sources: Aeillo 1998, Stott 1998, OIE: Manual of standards (see References).

Laboratory Diagnosis

Agent Isolation

• Sheep inoculation
• Embryonated chicken egg inoculation

Agent Identification

• Plaque reduction serum neutralization (can be used for serotype identification)

Serologic Tests

Animals typically seroconvert between 7 and 14 days after infection.

• Monoclonal-based competitive enzyme-linked immunosorbent assay (ELISA) (able to distinguish between genetically similar epizootic hemorrhagic disease viruses)
• Agar gel immunodiffusion
• Reverse transcriptase polymerase chain reaction (PCR) (can be used for serotype identification)
• Nested PCR is serotype-specific for BTV and EHDV and provides for rapid and cost-efficent differentiation (see References: Aradaib 2003, Wilson 1999)
• Virus neutralization
• Complement fixation

Specimen Collection and Submission for Diagnosis
Animal Status	Sample Type
Live animals	—Blood in heparin washed in antibiotic saline and resuspended in saline (for reduction of antibody neutralization if red cell lysis occurs) —Precolostrum serum in congenitally infected animals
Necropsy specimens*	—Spleen —Liver —Bone marrow —Lymph nodes
*Specimens should be shipped refrigerated, not frozen or fixed, to allow for isolation. Adapted from OIE: Manual of standards; Stott 1998 (see References).

Treatment

There is no specific treatment for bluetongue disease. Anti-inflammatory and pain relief medications can be used to limit symptoms.

Prevention

• Protection of bluetongue-free areas
• Border animal movement control
• Quarantine of imported animals.
• Control of vectors (especially in transportation)
• Routine serologic surveys of susceptible populations

Sources: DEFRA: Technical report; OIE: Manual of standards (see References).

Control

• Limiting vector exposure, number, and habitat can help control virus transmission (these practices apply to all animal production facilities, not just those of susceptible species):
• Keep animals indoors during peak vector times and conditions (from dusk to dawn); vectors may be active during daytime when overcast and in shady areas).
• Reduce vector habitat by changing water levels weekly and removing organic matter (manure) regularly.
• Use vector repellents like diethyltoluamide (DEET).
• Use larvacides in breeding sites.
• Satellite imagery is being evaluated to model vector population and coverage (see References: Baylis 1999).

Sources: DEFRA: Bluetongue disease control strategy; OIE: Manual of standards (see References).

Vaccination

• Vaccination with a modified live vaccine (serial passage through eggs or cell culture) is available and is typically used in endemic areas.
• A monovalent (serotype 10) vaccine is available for use in the United States for sheep; California has strains 10, 11, and 17 available.
• The vaccine carries some risks for pregnant animals.
• It is hypothesized that the virus may be transmissible to the vector through the vaccine and may reassort in the vector, so vaccine should be administered outside of peak Culcoides season.
• The vaccination serotype must correspond with the serotype of the virus in the field.
• VP2 (protein that induces neutralizing antibodies) has been studied as a candidate for recombinant vaccine.

Sources: Aeillo 1998, Stott 1998, OIE: Manual of standards (see References).

Public Health Issues

Bluetongue disease does not cause infection in humans; therefore, there are no public health issues to be considered.

References

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

Aradaib I, Smith WL, Osburn BI, et al. A multiplex PCR for simultaneous detection and differentiation of North American serotypes of bluetongue and epizootic hemorrhagic disease virus. Comp Immunol Microbiol Infect Dis 2003 Mar;26(2):77-87 [Abstract]

Baylis M, Meiswinkel R, Venter GJ. A preliminary attempt to use climate data and satellite imagery to model the abundance and distribution of Culicoides imicola in Southern Africa. S Afr Vet J 1999 Jun;70:80-9 [Abstract]

DEFRA (Department for the Environment Food and Rural Affairs, United Kingdom). Bluetongue disease control strategy [Web page]

DEFRA (Department for the Environment Food and Rural Affairs. United Kingdom). Bluetongue: pictures [Web page]

DEFRA (Department for the Environment Food and Rural Affairs, United Kingdom). Technical report: bluetongue. Nov 21, 2002 [Full text]

FAO (Food and Agricultural Organization of the United Nations). Update on vector-borne disease in the Mediterranean basin [Web page]

Fu H, Leake CJ, Metens PP, et al. The barriers to bluetongue virus infection, dissemination and transmission in the vector, Culicoides variipennis. Comp Immunol Microbiol Infect Dis 1999;144:747-61

Kahrs RF. Impact of bluetongue on international trade. Committee on Bluetongue and Bovine Retrovirus, US Animal Health Association. 1998 Proceedings

MacLachlan NJ, Pierce CM, de Mattos CA, et al. Evolution of bluetongue in the western United States. Committee on Bluetongue and Bovine Retrovirus, US Animal Health Association. 1997 Proceedings

Murphy FA, Gibbs EP, Horzinek MC, et al. Reoviridae. In: Veterinary virology. Ed 3. San Diego, CA: Academic Press, 1999

Odeon AC, Gershwin LJ, Osburn B. IgE responses to bluetongue virus serotype 11 after immunization with inactivated BTV and challenge infection. Comp Immunol Microbiol Infect Dis 1999 Apr;22(2):145-62 [Abstract]

OIE (Office International des Epizooties/World Organization for Animal Health). Bluetongue. In: Manual of standards for diagnostic tests and vaccines. Ed 4. Chap 2.1.9. Paris: OIE, 2000 [Full text]

OIE (Office International des Epizooties/World Organization for Animal Health). Bluetongue. Technical disease card database [Web page]

OIE (Office International des Epizooties/World Organization for Animal Health). Disease information in the last 18 months (recent outbreaks) [Web page—scroll to Bluetongue]

Singer RS, MacLachlan NJ, Carpenter TE. Maximal predicted duration of viremia in bluetongue virus infected cattle. J Vet Diagn Invest 2001;13:43-9 [Abstract]

Stott JL. Bluetongue and epizootic hemorrhagic disease. In: US Animal Health Association, Committee on Foreign Animal Disease. Foreign animal diseases: the gray book. Ed 6. Part IV. Richmond, VA: US Animal Health Association, 1998 [Full text]

USAHA (US Animal Health Association). Committee on Bluetongue and Bovine Retrovirus. Committee report. Oct 21, 2002]

Wilbur LA, Evermann JF, Mertens PP, et al. Abortion and death in pregnant bitches associated with a canine vaccine contaminated with bluetongue virus. J Am Vet Med Assoc 1994;204:1762-5

Wilson W. Preliminary description of a polymerase chain reaction test for bluetongue and epizootic hemorrhagic disease viral RNA in bovine serum. J Vet Diagn Invest 1999;11:337-79