African Horse Sickness

Published September 26, 2004

Agent
Hosts
Epidemiology
African Horse Sickness As a Biological Weapon
Clinical Features
Differential Diagnosis
Laboratory Features
Treatment
Prevention and Control
Public Health Issues
References

Agent

African horse sickness (AHS), a disease transmitted by an arthropod-borne virus, affects Equidaes in areas endemic for certain Culicoides midges or gnats. African horse sickness virus (AHSV) is an infectious, life-threatening, viscerotropic virus that can cause disease characterized by fever, vascular leakage, and a high rate of mortality.

Viral Classification

• Family: Reoviridae
• Genus: Orbivirus
• Nine serotypes (1-9)
• Phylogenetically similar to bluetongue virus in ruminants
• Synonyms: pestis equorum, peste equina, perdesiekte

Virion Morphology

• Nonenveloped
• Outer, middle, and inner capsids
• Spherical
• 55 to 70 nm in diameter (see References: Aiello)

Genetic Composition

• Double-stranded RNA (possesses all required enzymes for dsRNA transcription)
• Segmented (10 segments)
• 18 kilobases

Environmental Survival

Inactivation of AHSV can be accomplished in several ways, as shown in the following table.

Environmental Survivability of African Horse Sickness Virus
Condition	Survivability
Temperature	Can survive at room temperature for >1 mo (370C for 37 days) Inactivated by temperatures >500C for 3 hr, 600C for 15 min, 700C for 5 min Stable for up to 20 yr at 40C; however, inactivated by repeated freezing and thawing
pH	Viable at basic pH range: 6.3-12.0 (optimal, 6.5-8.5)
Chemicals/disinfectants	Inactivated by: Ether Beta-propiolactone 0.4% Phenol Iodophores Acetic acid, 2% Formalin 0.1%/48 hr Chlorine dioxide
Physical	Inactivated by radiation
Adapted from Erasmus 1998 (see References).

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Hosts

• African horse sickness is a seasonal disease of mainly Equidaes in sub-Saharan Africa, where the virus is endemic.
• Clinical disease can be evident in many Equidae species, all of which are considered accidental hosts:
• Horses
• Mules
• Donkeys
• Zebras, the only Equidae species native to South Africa, can remain viremic for up to 6 weeks post infection, potentially amplifying virus spread (see References: Barnard 1998). It is improbable, however, that the Zebra is responsible for long-term persistence of the virus, because of the relatively short viremia.
• Several other species in wild populations may harbor the virus without showing clinical disease, although it is unlikely that they serve as reservoirs:
• Zebras
• Elephants
• Onagers
• Camels
• Dogs can be infected, presumably by eating contaminated meat or animal products, and suffer severe clinical disease. Reports exist of dogs becoming infected via arthropod transmission in the 1990 Spanish outbreak (see References: Erasmus 1998).
• Humans have not been infected by field strains of the virus; however, occasional intranasal exposure to some vaccine strains has occurred (see References: Erasmus 1998).

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Epidemiology

AHSV was first recorded south of the Sahara Desert in the mid 1600s with the introduction of horses to southern Africa. The virus is considered endemic to the equatorial, eastern, and southern regions of Africa. Several outbreaks have occurred in Equidaes throughout Africa and elsewhere.

African Horse Sickness Virus Outbreaks
Location	Year	Serotype
Throughout Africa	Outbreaks appear about every 20 yr	All
Egypt, Palestine, Syria, Jordan	1944	3
Israel, Iran, Pakistan, Afganistan	1959	9
Israel, Iran, Pakistan, Afganistan, India, Turkey, Iraq, Syria, Lebanon, Jordan, Cyprus	1960	9
India, Pakistan, Turkey, Iran, Jordan, Iraq	1961	9
Algeria, Morocco, Tunisia, Spain	1965-1966	9
Pakistan	1974	Undetermined
Saudi Arabia	1975	Undetermined
Yemen	1980-1981	Undetermined
Spain	1987-1990	4
Morocco	1989-1991	4
South Africa	1996	2,* 4*
*80% of deaths due to serotypes 2 and 4. Adapted from Erasmus 1998; House 1993; Martmnez-Torrecuadrada 200; Meiswinkel 1998 (see References).

The disease, although infectious, is not transmitted directly between horses. Rather, transmission is via the biting Dipteran genus Culicoides (see References: Bouayoune 1998, Ortega 1998):

• C imicola (only proven vector)
• C obsoletus (suspected vector)
• C pulicaris (suspected vector)

Biting midges are necessary for the life cycle of the virus. In order for AHSV to become infective, it must be taken up in a blood meal from an infected host. After the virus matures within the arthropod vector, it can be introduced into a susceptible host at the following blood meal. Once inside the new host, the virus replicates in the local lymph nodes. Viremia and dissemination follow. The virus is present in high concentration within the blood and organs such as the spleen, lung, and lymph nodes. Traces of virus are found in serum, interstitial fluid, and bodily secretions (see References: Erasmus 1998, OIE).

Transmission within Africa is attributed to Culicoides dispersal. Optimal conditions of moist, warm weather complemented by plenty of rainfall and wind are found in the summer season, when the insect is most active. However, during the harsh winter months, the virus must survive in an appropriate reservoir. This overwintering period is longer than the duration of any known viremia, suggesting that the natural reservoir has not yet been discovered. Furthermore, in regions where the virus is not endemic, outbreaks are not persistent. Most likely, the inability of the virus to escape unfavorable conditions is due to the unavailability of the offending reservoir. Northward, the Sahara Desert partially impedes the virus from infecting nearby regions. Occasionally, AHSV can travel along waterways (eg, Nile River), to reach northern destinations. Introduction to naive regions more commonly occurs by importation of animals with subclinical disease, such as zebras. This was likely the case in the 1987-1990 Spain outbreak (see References: Erasmus 1998, DEFRA).

Morbidity depends on the number of infected Culicoides insects as well as the duration of exposure. Mortality varies depending on serotype, previous exposure, and species affected.

African Horse Sickness Mortality Rates
Species	Mortality Rate
Horses	70%-95% (naive herds)
Mules	50%
European/Asian donkeys	5%-10%
African donkeys	None evident
Zebras	None evident
Adapted from Africa News Service 1999, OIE, Erasmus 1998 (see References).

Outbreaks of AHS often result in significant equine losses; an estimated 300,000 animals died or were destroyed in the Middle Eastern 1959-1960 outbreak alone. The most recent outbreak in South Africa resulted in 500 equine deaths (see References: House 1993, Meiswinkel 1998).

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African Horse Sickness Virus As a Biological Weapon

AHSV has several qualities that make it a potential bioterrorism agent:

• Severity of disease
• High mortality rate among many Equidae species
• Arthropod vector to aid in dispersal
• Economic consequences associated with a devastated equine industry
• Lack of effective treatment

However, the failure of AHSV to persist in alien regions and its narrow host range, lasting immunity, and low zoonotic potential render the virus less than ideal for widespread consequences.

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Clinical Features

AHSV fever is a seasonal, viscerotropic disease characterized by subcutaneous/pleural edema and fever. The virus is manifested in several forms: peracute, subacute, acute, and horse sickness. Often, the associated respiratory and circulatory distress results in severe disease and death. Severity of disease varies among species, with horses being the most affected, followed in order by mules, donkeys, and zebras.

Horses

Clinical signs of AHS in horses are often confused with those of other diseases; however, AHSV should always be considered during the appropriate season when some or all of signs outlined in the table below are present.

Clinical Features of African Horse Sickness Virus in the Horse*
Form	Characteristics
Peracute (pulmonary)	Shorter incubation period (3-5 days) Highest mortality (95%) Characterized by acute, rapidly progressive pulmonary involvement Disease course 1-3 days Clinical appearance (listed in general order of appearance): ~Fever (40-410C), lasting 1-2 days ~Congested ocular, nasal, and oral mucous membranes ~Increasing respiratory rate (up to 60 bpm) ~Wide abnormal stance, with head and neck extension ~Flared nostrils ~Forced expiration resulting in heave lines ~Profuse sweating common ~Spasmadic cough ~Frothy, serofibrinous, potentially blood-tinged fluid may exude from nostrils (see Gray Book Figure [References: Erasmus]) ~Sudden- onset dyspnea ~Death due to anoxia (follows closely after dyspnea onset)
Subacute (cardiac)	Incubation period 7-14 days Lower mortality (50%-60%) Edematous swelling of facial tissues and cardiac failure Disease course 3-8 days Clinical characteristics (listed in general order of appearance): ~Fever (39-410C), lasting 3-6 days ~Edema of the supraorbital fossa (pathognomic for this form (see Gray Book Figure [References: Erasmus]), eyelids, lips, cheeks, intermandibular space, tongue, laryngeal region, jugular groove, brisket ~Petechial hemorrhage of conjunctiva and ventral tongue surface (see Gray Book Figure [References: Erasmus]) ~Depression ~Colic signs (may occur) ~Death due to cardiac failure
Acute (mixed)*	Incubation period 5-7 days Mortality rate 50%-90% Characterized by combination of peracute and subacute syndromes Disease course about 1 wk Clinical appearance (listed in general order of appearance): ~Nonprogressive pulmonary distress ~Edema ~Death due to cardiac failure
Horse sickness	Often not detected, as this is the mildest and often subclinical form High recovery rates Characterized by fever Can occur in partially immune animals (ie, vaccinated with or exposed to heterologous serotype) Disease course 3-8 days Clinical appearance: ~Remittent fever (rarely above 400C), with low temperature in morning hours and peak temperature in afternoon Other symptoms (may or may not be present): slight congestion of conjunctivae, increased pulse, mild anorexia, mild depression
*Most common form of the disease. Adapted from Erasmus 1998; DEFRA; House 1993; Aiello 1998 (see References).

Other Animals

• The clinical disease in mules often resembles that in horses. Donkeys and zebras, however, usually manifest the horse sickness form of the disease and mortality is significantly lower than for horses. The viremic period typically is 4 to 8 days in horses but in donkeys can be as long as 28 days and in zebras can be between 28 and 43 days (see References: Erasmus 1998).
• Affected dogs exhibit the pulmonary form of the disease (see References: Aiello 1998).
• The gross pathology of AHSV that may be found in varying degrees at necropsy is shown in the table below.

Necropsy Features of African Horse Sickness Virus in the Horse*
Form	Characteristics
Peracute (pulmonary)	Severe lung edema 1 Alveolar edema 1 Interstitial edema 1 Subpleural edema Frothy exudate in trachea, bronchi, and bronchioles Mottled pleural hyperemia Hydrothorax (several liters of straw-colored fluid) Edematous lymph nodes of thoracic and abdominal cavities Congestion of glandular fundus of stomach and possibly renal cortex Intestinal petechiae in mucosal and serosal surface
Subacute (cardiac)	Yellow, gelatinous infiltrate of subcutaneous and intermuscular fascia (see Gray Book Figure [References: Erasmus]) ~Head ~Neck ~Shoulders ~Local lymph nodes ~Ligamentum nuchae Submucosal edema ~Cecum ~Large colon ~Rectum ~Hydropericardium (~2 L straw-colored fluid) Petechial to ecchymotic hemorrhages ~Epicardium ~Endocardium ~Ventral tongue ~Peritoneum ~Intestinal serosal surface Myocarditis Hemorrhagic gastritis and enteritis Lungs may be heavy or engorged Hemorrhage at junction of papillary muscle and chordae tendinae may also be seen
Acute (mixed)	Pathology in acute form of disease is represented by combination of the lesions in pulmonary and cardiac forms, predominated by one type or the other
Horse sickness fever	Pathologic changes seen at necropsy is rare, considering most animals displaying this form recover
Adapted from Erasmus 1998, DEFRA, House 1993, OIE, Aiello 1998 (see References).

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Differential Diagnosis

Clinical signs associated with AHSV are clearly not pathognomic. Other diseases to consider are listed below (see References: OIE; Erasmus 1998):

• Viral
• Equine infectious anemia (Retroviridae)
• Equine viral arteritis (Arteriviridae)
• Equine encephalosis (Reoviridae) (often occurs concurrently with AHSV; differentiable by absence of edema and lower mortality rates)
• Bacterial
• Anthrax (Bacillus anthracis)
• Protozoan
• Trypanosomiasis (Trypanosoma evansi)
• Piroplasmosis (Babesia caballi and Babesia equi)
• Other
• Purpura haemorrhagica (lesions on necropsy tend to be more widely distributed in this condition than in AHS)

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Laboratory Diagnosis

Field diagnosis is difficult because AHS can be easily confused with other diseases. Presumptive diagnosis can be made based on seasonality, clinical signs, and necropsy lesions. However, proper diagnosis must be made with laboratory techniques to confirm that AHSV is present. Procedures and associated recommendations are listed in the table below.

Diagnostic Procedures and Recommendations to Confirm African Horse Sickness Virus
Diagnostic Procedure	Specific Test
Virus isolation*	Intracerebral inoculation of suckling mice Intravenous inoculation of embryonated eggs Cell culture (BHK21 or Vero cells)
Virus identification	ELISA Virus neutralization RT-PCR
Serology**	ELISA Complement fixation Immunoblotting (allows for differentiation between infection and vaccination) Hemagglutination inhibition
Sample collection recommendations	Blood from febrile animal should be placed in an OPG/OCG solution (50% glycerol, 0.5% potassium oxalate, 0.5% phenol) or heparinized (10 IU/mL) Fresh tissue samples taken at necropsy from spleen, lung, and lymph node and preserved in 10% buffered glycerine Both blood and tissue samples should be stored and transported at 40C (never frozen)
Abbreviations: ELISA, enzyme-linked immunosorbent assay; RT-PCR, reverse transcriptase-polymerase chain reaction. *More than one system recommended because incubation time in mice may be quite long. **AHS antibodies are detectable about 10 to 14 days post infection and remain present 1 to 4 yr. Adapted from: Erasmus 1998; Aiello 1998, Zientara 1998 (see References).

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Treatment

No specific treatment is available for AHS. Recovered animals demonstrate life-long immunity to that serotype and partial immunity to similar serotypes. Passive immunity from maternal antibodies lasts about 6 months.

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Prevention and Control

Prevention in Naive or Nonendemic Countries

Disease-free countries can protect themselves through strict 60-day quarantine of animals, especially Equidae species, imported from endemic regions. Also, serologic testing of imported animals may be helpful, since zebras and some donkeys may never display clinical illness. When performing serotype analysis, however, caution must be taken so as not to confuse vaccinated animals with infected animals.

Control Strategies Following AHSV Outbreak

Once a locus of clinical disease has been recognized, a prompt response is necessary to control the disease. Potential Culicoides vectors exist in most countries; therefore, local transmission could theoretically transpire. Several steps are recommended to halt disease spread (see References: DEFRA; Erasmus 1998):

• Recognition and isolation of causative agent (subclinical, imported animal versus Culicoides introduction)
• Determination of virus serotype in order to obtain proper vaccine
• Timely slaughter and disposal of all infected animals
• Development of
• Control zone: 100-km radius from infected premise for 1 year
• Surveillance zone: 150-km radius from infected premise for 1 year
• Restriction of movement into and out of protected areas
• Careful monitoring of individual Equidae vital signs in areas with known infection (rectal temperature, taken twice daily, may help predict onset of infection)
• Slaughting or isolating febrile animals in insect-free area until cause is determined to prevent further dissemination

Other general preventive measures that may help reduce the risk of disease transmission include:

• Vaccination of susceptible animals (see Vaccination Programs below)
• Vector control
• Insecticides
• Repellents
• Screens
• Reduction of exposure to arthropod vector: Keep horses in stables or barns from dusk till dawn, because Culicoides species are most active at sunrise and sunset (see References: Erasmus 1998).

Vaccination Programs

Vaccination programs have been a major method of combatting AHSV. Because both horses and donkeys can be viremic, it is essential for control programs to include both species in vaccination protocols. Vaccination is only beneficial, however, as prophylaxis(see References: Erasmus 1998; Lord 1997; OIE).

• Several factors are important in regard to attenuated vaccines:
• They do not allow for differentiation between vaccinated and infected animals and may aid in persistence of the virus (see Reference: Martinez-Torrecuadrada 2001).
• The original attenuated vaccine occasionally caused encephalitis in horses.
• The newer, quadrivalent vaccines given 3 weeks apart are commonly given.
• Monovalent vaccines are useful, especially in nonendemic regions, where the causative agent is a known, single serotype.
• Monovalent inactivated vaccines are only available for serotype 4.
• Research continues to provide differential polyvalent vaccines.

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Public Health Issues

The clinical disease in humans, transmitted by intranasal exposure to certain neurotropic vaccines, is represented by varying degrees of encephalitis, chorioretinitis, and coagulopathy (see References: Erasmus 1998; Swanepoel 1992).

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References

Africa News Service. African horse sicknessSouth Africa. Mar 29, 1999

Aiello SE. African horse sickness. In: Merck veterinary manual. Ed 8. Whitehouse Station, NJ: Merck & Co, 1998:496-8 [Full text]

Barnard BJ. Epidemiology of African horse sickness and the role of the zebra in South Africa. Arch Virol 1998;14:13-19 [Abstract]

Basak AK, Gouet P, Grimes J, et al. Crystal structure of the top domain of African horse sickness virus VP7: comparisons with bluetongue virus VP7. J Virol 1996 Jun;70(6):3797-806 [Full text]

Bouayoune H, el Hasnaoui H, Baylis M, et al. The Culicoides vectors of African horse sickness virus in Morocco: distribution and epidemiological implications. Arch Virol 1998;14:113-25 [Abstract]

Bougrine SI, Fihri OF, Fehri MM. Western immunoblotting as a method for the detection of African horse sickness virus protein-specific antibodies: differentiation between infected and vaccinated horses. Arch Virol Suppl 1998;14:329-36 [Abstract]

DEFRA (Department for Environment Food and Rural Affairs). Disease surveillance and control: African horse sickness [Web page]

Erasmus BJ. African horse sickness. 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 Assoc, 1998 [Full text]

House JA. African horse sickness. Vet Clin North Am Equine Pract 1993;9(2):355-64 [Abstract]

Lord CC. Simulation studies of vaccination strategies in African horse sickness. Vaccine 1997;15(5):519-24 [Abstract]

Martmnez-Torrecuadrada JL. Definition of neutralizing sites on African horse sickness virus serotype 4 VP2 at the level of peptides. J Gen Virol 2001;82:2415-24 [Full text]

Meiswinkel R. The 1996 outbreak of African horse sickness in South Africa - The entomological perspective. Arch Virol 1998;14:69-83 [Abstract]

OIE (Office International des Epizooties/World Organization for Animal Health). African horse disease. Technical disease card database [Full text]

Ortega MD, Mellor PS, Rawlings P, et al. The seasonal and geographical distribution of Culicoides imicola, C. pulicaris group and C. obsoletus group biting midges in central and southern Spain. Arch Virol 1998;14:85-91 [Abstract]

Swanepoel R. Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers: virological and serological investigations. S Afr Med J 1992 May 2;81(9):458-61 [Abstract]

Zientara S, Sailleau C, Moulay S, et al. Use of reverse transcriptase polymerase chain reaction (RT-PCR) and dot-blot hybrididation for the detection and identification of African horse sickness virus nucleic acids. Arch Virol Suppl 1998;14:317-27 [Abstract]

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