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African Horse Sickness
UPDATE ON INFECTIOUS DISEASES
0749-0739/93 $0.00 + .20
AFRICAN HORSE SICKNESS James A. House, DVM, PhD
African horse sickness (AHS) is a peracute, acute, subacute, or mild (horsesickness fever) disease of Equidae that causes mortality by inducing pathologic changes in the circulatory and respiratory systems. African horse sickness viruses (AH5V), of which there are nine serotypes, are biologically transmitted in nature by Culicoides spp and, perhaps, by mosquitoes.
HISTORICAL ASPECTS
AHS was first described by Theiler50 in 1921, when he related seven major epizootics of AHS in the Cape Province of South Africa between 1780 and 1918. The disease is endemic in sub-Saharan Africa; it occurs annually or seasonally wherever susceptible Equidae are present. 50 On numerous occasions, AHS has spread outside of its usual sub-Saharan African niche. In 1944, AHS serotype 3 spread from Egypt to Palestine, Syria, and Jordan.2 The most extensive epizootic, which was caused by serotype 9, occurred during 1959 to 1960. The disease occurred in Iran, West Pakistan, and Afghanistan in the summer of 1959. The virus apparently over-wintered and spread to Jordan, India, Turkey, Cyprus, Iraq, Syria, and Lebanon in 1960. It is estimated that 300,000 Equidae died or were destroyed during this epizootic. 20 ,'3 Another epizootic of AHS, caused by serotype 9, occurred in Algeria, Morocco, Tunisia, and Spain during 1965 to 1966?' 28 Local outbreaks of AHS, whose serotype has not been determined, have been reported in Pakistan (1974), Saudi Arabia (1975), and Yemen (1980-1991),41 In 1989, AHS (serotype 9) was reported in Saudi Arabia,1 The most recent outbreaks of AHS outside of sub-Saharan Africa were in Spain from 1987 to 1990,>1,31,32,35 Portugal in 1989,33 and Morocco in 1989 to 1990,34,36 The disease has not occurred in Spain or Portugal in 1991 or 1992,
From the United States Department of Agriculture, Animal and Plant Health Inspection Service, National Veterinary Service Laboratories, Veterinary Services, Foreign Animal Disease Diagnostic Laboratory, Greenport, New York
VETERINARY CLINICS OF NORTH AMERICA: EQUINE PRACTICE VOLUME 9 • NUMBER 2 • AUGUST 1993
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VIRAL CHARACTERISTICS
AHS was shown to be caused by a filterable agent in 1900 by M'Fadyean.22 AHS is caused by viruses in the family Reoviridae, the genus Orbivirus, the subgroup AHSV, of which there are nine serotypes. 20. 26 The orbiviruses contain 10 segments of double-stranded RNA surrounded by two layers of viral cap someres.24 The AHSV is destroyed by heating to 70°C for 5 minutes, or to 50°C for 10 minutes.'8 The virus is rapidly inactivated by pH below 6.0. 3 These viruses are quite stable in blood when stored with various preservatives at refrigeration temperature. Other orbiviruses of veterinary importance are bluetongue, epizootic hemorrhagic disease, equine encephalosis, and Chuzan viruses.
EPIDEMIOLOGY Geographic Distribution
AHS has spread from its normal and current enzootic areas in sub-Saharan Africa on numerous occasions. The disease has been reported to occur sporadically in Pakistan (1974), Saudi Arabia (1975), and Yemen (1980-1981).4 1 It was reported in Saudi Arabia in 1989 ' and in Morocco in 198934 and 1990. 36 Thus, the Middle East is considered an active AHS area. Following the epizootics in Spain from 1987 through 1990, clinical cases have not been reported, but Spain has not been declared free of AHS by the USDA or Office International des Epizooties (OlE) as of June 1992. With the rapid movement of Equidae throughout the world, there is the distinct possibility that Equidae could leave a country where AHS was present but not yet diagnosed and enter the United States. The quarantine for Equidae coming into the United States from countries free of AHS is 5 to 7 days. This is within the incubation period of AHS, and such animals could legitimately pass through quarantine and into the mainland.
Transmission
African horse sickness is not a contagious disease; rather, it is arthropodborne and may spread to new areas via infected animals or vector movement. The principal vectors of AHS are Culicoides spp. Culicoides live in varied aquatic habitats, decaying vegetation or manure, low-lying areas, river basins and deltas, coastal areas, or swamps. Culicoides spend the vast majority of their life in the egg, larval, and pupal stages and overwinter this way. They feed from dusk to dawn, with the peak feeding times at twilight. Culicoides may generate several generations during a season, and the adult stages are normally present in the spring and summer with peak activity during the fall. Culicoides prefer not to enter buildings, and housing Equidae in barns diminishes the risk of their being bitten. DuToit' 2 detected AHSV in wild-caught Culicoides spp by inoculating a susceptible horse with a suspension of the insects. Further, he reported that he had experimentally transmitted AHSV using wild-caught culicoides. He fed Culicoides spp on an AHSV-infected horse, then fed it 12 days later on a susceptible horse that subsequently developed AHS.53 The vector competence of C. variipennis was substantiated in the laboratory by feeding gnats on infected embryonating
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chicken eggs and 1 week later refeeding the gnats on uninfected embryonating chicken eggs. 6 In Spain, ASHV-4 was isolated from pools of C. imicola and, for the first time, from pools of C. pulicaris and C. obsoletus with C. cataneii and C. lailae present as minority populations. It is of interest that "the range of both C. pulicaris and C. obsoletus probably extends much farther north and indeed these two species are probably the commonest midges in Northern Europe and the United Kingdom. 27 In endemic areas of Africa, the overwintering mechanism of the AHSV has not been clarified. Transovarial transmission of AHSV in culicoides has not been demonstrated. Possible means of viral survival suggested are that a yet-to-be determined reservoir host of AHSV may exist, or perhaps transovarial viral transmission may occur in unknown species of culicoides. Regarding overwintering, C. imicola has been found to survive "on the wing" the whole year in certain areas of Spain, providing a plausible mechanism for viral survival year to year. 27 Although culicoides are considered to be the major biological vector of AHSV, three species of mosquitoes have experimentally transmitted AHSV. 39,40 AHSV has been isolated from a camel tick, Hyalomma dromedarii, with the virus replicating through the developmental stages of this tick. 4 AHSV has been isolated from street dogs in Egypt.. Rhipicephalus sanguineus has been reported to transmit AHSV from sick dogs ·to susceptible dogs and horses, and from sick horses to susceptible dogs. Transovarial transmission of AHSV was not observed, but transtadial persistence of the virus from larva through the adult was reported. 9 Oral infection of dogs by ingestion of meat from AHSV-infected Equidae has been reported to cause mortality.5. 23. 49. 52 AHS may spread by insect movement. Evidence has been presented indicating that culicoides were carried 5 to 6 km46 and 40 to 700 km"s Although insects play the major role in transmission of AHSV, mechanical means such as by the use of contaminated surgical instruments and needles should be considered. Host Range
The natural host of AHS is Equidae. Dogs may become infected and suffer mortality by ingesting meat from AHSV-infected horses. s, 23. 49, 52 Camels have been reported to be infected with AHSV ..· 44 Among Equidae, horses are more susceptible than mules, which are more susceptible than donkeys, whereas zebras are the most resistant and show only minimal clinical signs. Naturally resistant horses may exist in north Africa and just south of the western Sahara.s Ancestors of these horses have been in the area since 2000 B.C. These animals were not vaccinated but had antibodies to AHSV without demonstrating any clinical sign of AHS.25 The African donkey is more resistant than donkeys in the Middle East, which suffered significant mortality in the 1944 epizootic.> Zebras are highly resistant to AHSV infection, and mortality is usually low.'" 16 CLINICAL ASPECTS Clinical Signs
AHS classically presents four clinical syndromes:'" 29, 50 the pulmonary or peracute form; the cardiac or subacute form; the mixed or acute form (presenting signs of the pulmonary and cardiac forms); and the horse sickness fever form.
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The peracute or pulmonary form has an incubation of 3 to 5 days and runs the shortest course, with animals presenting clinical signs for 1 to 3 days. The first clinical sign is fever (103°-105°P; 39S-40SC), followed by congestion of the mucous membranes of the eyes, nose, and mouth. Usually, within a few hours prior to death, animals become depressed and may have an increased respiratory rate (up to 60 or more per minute), profuse sweating, and spasmodic cough. During the terminal stage, frothy fluid (which may be blood-tinged) may exude from the nostrils. Auscultation may reveal lung edema and hydrothorax, as evidenced by moist rales and muffled heart sounds. Equidae may die peracutely without presenting significant clinical or pathologic changes. Mortality is about 95%. The subacute, edematous, or cardiac form has an incubation from 7 to 14 days, with the course of the disease lasting 3 to 6 days. The first sign is fever (101°105°P; 3SS-40'soC) followed by congestion of the mucous membranes of the eyes, nose, and mouth. Late in the clinical course, subcutaneous edema and edema in intermuscular fascia swellings may occur in the neck, jugular furrow, extensor muscles of thoracic and lumbar regions, and hip. Edema of the supraorbital fossa, which may cause it to bulge, is considered pathognomonic for the cardiac form. lO The eyelids and intermandibular space may develop edema. Animals usually continue to eat and drink throughout the course of the disease, although depression may occur toward the end of the syndrome. Petechial hemorrhages may occur on the ventral surface of the tongue and in the conjunctiva. Signs of colic are not uncommon. Death usually occurs 4 to 8 days after the onset of fever. Mortality is generally 50% in the cardiac form. The acute or mixed form has an incubation period of 5 to 7 days. This is the most common form of AHS and presents clinical signs of both the pulmonary and cardiac forms. Mortality ranges from 50% to 95%, and death usually occurs 3 to 6 days after the onset of fever. The horse sickness fever form is not commonly detected since it is a mild form of the disease; it is purported to occur in "partially immune" animals in endemic areas and resistant species such as the donkey and zebra. The incubation period ranges from 5 to 14 days. A low-grade fever (101°-103°P; 3SS-39'soC) may be detected, especially in the afternoon, for a period of 5 to S days. The conjunctiva may be congested, and there may be a slight anorexia and depression. Animals affected with the horse sickness fever form recover. The most consistent signs common to all the forms of AHS are fever and congestion of the ocular, nasal, and oral mucous membranes. The distribution of clinical signs for the different forms of AHS is compared in Table 1.
Pathology
The gross pathology of the various forms of AHS has been well-described.!4, In the necropsy of Equidae in which clinical and epidemiologic signs suggest AHS, the first procedure is to reflect the skin from the thorax, neck, and head to examine for subcutaneous edema. Next, carefully dissect the muscle bundles and fascia, looking for intermuscular fascial edema in the neck, extensor muscles of thoracic and lumbar regions, and intercostal areas. The area adjacent to the ligamentum nuchae and jugular furrows are sites of predilection for edema caused by AHSV infection. Pathologic changes observed in the pulmonary form include severe lung edema and hydrothorax, with several liters of straw-colored fluid present in the thorax. Lung edema is present when the interlobular septae are grossly visible 29, 50
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Table 1. POSSIBLE CLINICAL SIGNS AFRICAN HORSE SICKNESS
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IN THE DIFFERENT FORMS OF Form of the Disease
Clinical sign Nonpurulent conjunctivitis Fever Congested nasal and oral mucous membranes Increased respiratory rate Moist rales Muffled heart sounds Edema of the neck Edema of the supraorbital fossa Colic
Pulmonary Yes Yes Yes
Cardiac Yes Yes Yes
Mixed Yes Yes Yes
Horse Fever Yes Yes Yes
Yes Yes Yes No No No
Yes Yes Yes Yes Yes Yes
Yes Yes Yes Yes Yes Yes
Rare No No No No No
and the pleura presents a glassy appearance (subpleural edema). There may be petechial hemorrhages on the lungs and periaortic edema. Lymph nodes of the thoracic and abdominal cavities may be edematous. The gland~lar portion of the stomach may be congested, and there may be petechiae in the serosae of the intestines. In the cardiac form, edema may occur in the subcutaneous tissues of the thorax, neck, intermuscular areas of the neck, intercostal muscles, extensor muscles of thoracic and lumbar regions, deep muscles of the hip, and lymph nodes. Hydropericardium is observed with up to 2 L or more of straw-colored fluid present. There may be petechial and ecchymotic hemorrhages in the epicardium and endocardium; the significance of these is controversial. Hemorrhages may be observed in the papillary muscles near the junction with the chordae tendineae. The lungs may be slightly heavier than normal. There may be petechial hemorrhages in the serosa of the intestines. The pathologic changes in the mixed form of AHS are a combination of those described for the pulmonary and cardiac forms, but usually there are more significant pathologic changes in the lungs or extensive edema, indicating predominance of either the pulmonary or cardiac form, respectively. Microscopic changes in the lungs include edema fluid containing fibrin and inflammatory cells suggestive of an exudative pneumonia.>9 There is depletion of lymphoid cells and necrosis of germinal centers in the spleen and lymph nodes. Centrilobular congestion of the liver lobules with hydropic degeneration of hepatocytes is commonly observed.
DIAGNOSIS AND PROGNOSIS
A disease of Equidae causing high mortality, lung edema, subcutaneous and intermuscular edema, occurring during the time of year when culicoides are active (spring, summer, but mainly autumn) should evoke a presumptive diagnosis of AHS. Some regard edema of the supraorbital fossae as pathognomonic for the cardiac form of AHS.1O When AHS is suspected, contact the state or Federal veterinary officials immediately. They will arrange for a foreign animal disease diagnostician to visit the premises, examine the animals, gather epidemiologic information, necropsy animals, advise on quarantines, and send samples to the USDA's Foreign Animal
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Disease Diagnostic Laboratory (FADDL) at Plum Island, New York. The FADDL is the only diagnostic laboratory in the United States that is allowed to work with AHSV; all AHS diagnostic tests are performed there. Differential diagnoses include equine infectious anemia, equine viral arteritis, equine piroplasmosis (babesiosis), equine influenza, purpura hemorrhagica, equine rhinopneumonitis, ingestion of poisonous plants such as Crotalaria, and colic. Virus isolation via the intracranial inoculation of suckling mice 1 to 3 days of age, inoculation of BHK-21 or Vero cells, and intravenous inoculation of 10- to 12-day embryonating chicken eggs (ECE) are used for the isolation of AHSV. Virus is identified by group reactive tests such as complement fixation, indirect fluorescent antibody, or enzyme-linked immunosorbent assay (ELISA) . The specific serotype is identified by virus neutralization using serotype-specific serums. Serologically, group reactive antibody (reacting against all nine serotypes) can be detected by the agar gel immunodiffusion, indirect fluorescent antibody, complement fixation, and ELISA. Type specific antibody is measured by VN. ' 8 There is no specific treatment for AHS. Mortality varies from 50% to over 95%. The highest mortality occurs in the peracute pulmonary form. In endemic areas "natural resistance," especially in donkeys and zebras, and vaccination may ameliorate or prevent the disease.
PREVENTION AND CONTROL
The philosophy for the control of AHS differs for endemic areas, where unknown reservoirs of the AHSV may exist, and nonendemic areas. In a nonendemic area, the goal is to eradicate the disease, whereas in an endemic area, the main thrust of regulatory efforts is directed at preventing losses from the disease. In the United States "The goal of disease prevention and control is to contain ASH in as small a geographic area as pOSSible, and rapidly and efficiently eradicate it from the United States. Expanse of affected areas will depend on timeliness of virus detection, distribution and population density of the insect vectors, and movement of equines. Early detection of the virus combined with prompt initiation of quarantine and vector control are critical to limiting the spread and permitting disease eradication."s1 Other actions include "Take immediate action after detection of AHS virus to eliminate contact between susceptible animals and known insect vectors. Destroy and properly dispose of, or place in Culicoidesproof enclosures, all diseased animals. Prohibit movement of susceptible animals from the affected premises and the areas of possible infected vector activity by issuance of quarantines and taking required enforcement actions."s1 There would be significant discourse with representatives of the equine industry concerning the outbreak. In the United States, an emergency disease declaration would be made, an emergency disease eradication network (Regional Emergency Animal Disease Eradication Organization "READEO") would be called into action, all movements of Equidae would be traced back, and vaccination would be initiated if the former actions did not control and eradicate the disease. To keep diagnostic preparedness at peak, the USDA has a cadre of about 300 foreign animal disease diagnosticians active to assist in diagnosis, epidemiologic examinations, and sampling of suspect cases of AHS. These diagnosticians are veterinarians trained in field diagnosis at the FADDL during annual foreign animal disease training courses where 14 foreign animal diseases, including AHS, are demonstrated in their natural hosts.
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In AHS endemic areas of Africa, vaccines have been developed and used successfully to control losses from AHS. The first vaccines were modified live vaccines (ML V) of high adult mouse brain passage. 3 These neurotropic vaccines were, in many cases, effective for the prevention of clinical disease and death, but some of the vaccines against certain serotypes were not effective,!9 and others had the potential to produce encephalitis in horses and donkeys.30. 4 2, 47 Erasmus13 showed that these vaccines caused encephalitis in guinea pigs when administered intranasally. Cell-culture ML V vaccines were developed that were reported to be efficacious; no safety problem was described. ls These cell-culture vaccines are now in use in South Africa and were used in Spain in 1987 to 1990. The cell culture MLV against serotype 4 of AHS did not produce a detectible viremia in vaccinated Equidae, and it did protect against clinical disease in vaccinates that were challenge-inoculated with virulent AHSV-4. A potential weakness of these vaccines is that they may not prevent viremia in vaccinates that are exposed to virulent AHSV. One of three vaccinates challenge-inoculated with virulent AHSV-4 had a viremia (10 2 1 to 104 8 infectious particies/mL of blood between 3 to 11 days after challenge inoculation) quite similar to that found in nonimmune animals. A second pony had a viremia of 102.8 infectious particies/mL of blood. This was likely residual challenge virus. The third vaccinate had no detectible viremia following challenge inoculation.17 A commercial inactivated AHS vaccine was recently developed (Dubourget P, Preaud JM, Detraz N, et al: Development, production and quality control of an industrial inactivated vaccine against AHS type IV. Submitted for publication, 1991). One dose prevented death of nine of nine vaccinates and prevented clinical signs in six of nine vaccinates. A viremia between 1026 and 103.1 infectious AHSV particies/mL of blood occurred for 3 days in one of nine vaccinates. All three control ponies died following challenge inoculation and had viremias > 10s0 infectious AHSV particies/mL of blood (House JA, Lombard M, House C, et al: Efficacy of an inactivated vaccine for African horse sickness serotype 4. Submitted for publication, 1991). A significant problem in evaluating the efficacy of vaccines for use in eradicating AHSV is that the threshold level of viremia that would allow the culicoides vector to become infected is unknown. Studies are currently underway at the FADDL to determine this. There are no reports of humans becoming infected with AHSV of field origin. Certain strains of neurotropic AHSV may cause encephalitis and chorioretinitis following intranasal exposure of humans to the virus. 48
SUMMARY
AHS is a noncontagious vector-borne disease of Equidae caused by Orbiviruses. Species susceptibility in decreasing order is horses, mules, donkeys, and zebras. The main vectors of AHS are culicoides. The disease is endemic in subSaharan Africa, but epizootics have occurred outside of this area on several occasions. The most recent outbreaks outside of the endemic area were in Spain, Morocco, and Portugal between 1987 and 1990. AHS causes mortality up to 95% and is classically divided into four clinical forms: the pulmonary, cardiac, mixed, and horse fever forms. Pathologic changes are subcutaneous and intermuscular edema and lung edema. The most consistent clinical signs include fever, nonpurulent conjunctivitis, and increased respiratory rate. Prevention and control measures include quarantines, control of insects, and vaccination. There is no treat-
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ment for AHS. Neurotropic strains of AHSV may cause retinitis and encephalitis in humans. References 1. Anderson EC, Mellor P, Hamblin C: African horse sickness in Saudi Arabia. Vet Rec 125:489, 1989 2. Alexander RA: The 1944 epizootic of horse sickness in the Middle East. Onderstepoort J Vet Res 53:471, 1948 3. Alexander RA, Dutoit PJ: The immunization of horses and mules against horse sickness by means of neurotropic virus of mice and guinea pigs. Onderstepoort J Vet Res 2:375, 1934 4. Awad FI, Amin MM, Salama SA, et al: The role played by Hyalomma dromedarii in the transmission of African horse sickness virus in Egypt. Bull Anim Health Prod Afr 29:337,1981 5. Bevan LEW: The transmission of African horse-sickness to the dog by feeding. Vet J 67:402,1911 6. Boorman J, Mellor P A, Penn M, et al: The growth of African horse-sickness virus in embryonated hen eggs and the transmission of virus by Culicoides variipennis Coquillet (Diptera, Ceratopogonidae). Arch ViroI47:343, 1975 7. Botija CS, Ordas A, Ovejero JA, et al: El Diagnostico de la peste equina en Espana. Bulletin Office International des Epizooties 68:695, 1967 8. Bourdin P: Ecology of African horsesickness. In Proceedings of the Third International Conference on Equine Infectious Diseases. Basel, S. Karger, 1973 p 12 9. Dardiri AH, Salama SA: African horsesickness: An overview. Equine Vet Sci 8:46-49, 1988 10. Dardiri AH: African horse sickness. Foreign animal diseases; their prevention diagnosis and control [Revised] . Richmond, VA, Committee on Foreign Animal Diseases of the United States Animal Health Association, 1984, p 23 11. Davies FG, Otieno S: Elephants and zebras as possible reservoir hosts for African horsesickness virus. Vet Rec 100:291, 1977 12. DuToit RM: The transmission of blue-tongue and horse-sickness by Culicoides. Onderstepoort J Vet Sci Anim Ind 19:7, 1944 13. Erasmus BJ: Preliminary observations on the value of the guinea-pig in determining the innocuity and antigenicity of neurotropic attenuated horsesickness strains. Onderstepoort J Vet Res 30:11, 1963 14. Erasmus BJ: The pathogenesis of African horsesickness. In Proceedings of the Third International Conference on Equine Infectious Diseases. Basel, S. Karger, 1973, p 1 15. Erasmus BJ: A new approach to polyvalent immunization against African horsesickness. In Proceedings of the Fourth International Conference on Equine Infectious Diseases. Lyon, Veterinary Publications, 1976, p 401 16. Erasmus BJ, Young E, Pieterse LM, et al: The susceptibility of zebra and elephants to African horsesickness virus. In Proc Fourth Int Conf Equine Infect Dis, Lyon, Veterinary Publications, 1976, p 409 17. House C, House JA, Mebus CA: A Review of African Horse Sickness with emphasis on selected vaccines. Tropical Veterinary Medicine: Current Issues and Perspectives. Ann NY Acad Sci 653:228,1992 18. House C, Mikiciuk PE, Berninger ML: Laboratory diagnosis of African horse sickness: Comparison of serological techniques and evaluation of storage methods of samples for virus isolation. J Vet Diagn Invest 2:44,1990 19. House JA, House C: Immunization studies on African horse sickness. In Proceedings of the 93rd Annual Meeting of the United States Animal Health Association, Las Vegas, 1989, p 356 20. Howell PG: The isolation and identification of further antigenic types of African horsesickness virus. Onderstepoort J Vet Res 29:139, 1962 21. Lubroth J: African horse sickness and the epizootic in Spain, 1987. Proc AAEP 33:871, 1988 22. M'Fadyean J: African horsesickness. J Comp Pathol Ther 13:1, 1900
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23. M'Fadyean J: The susceptibility of the dog to African horse-sickness. J Comp Pathol Ther 23:27, 1910 24. Matthews REF: Classification and nomenclature of viruses. Intervirology 17:1, 1982 25. Maurice Y, Provost A: La peste equine a type 9 en Afrique central. Enquete serologique. Rev Elev Med Vet Pays Trop 20:21, 1967 26. McIntosh BM: Immunological types of horsesickness virus and their significance in immunization. Onderstepoort J Vet Res 27:465, 1958 27. Mellor PS, Boned J, Hamblin C, et al: Isolations of African horse sickness virus from vector insects made during the 1988 epizootic in Spain. Epidemiol Infect 105:447, 1990 28. Montilla DR, Marti P: Epizootologia de la peste equina en Espana. Bulletin Office International des Epizooties 68:705, 1967 29. Newsholme SJ: A morphological study of the lesions of African horsesickness. Onderstepoort J Vet Res 50:7, 1983 30. Nobel TR, Neumann F: Vaccination against African horse sickness and post-vaccination reaction in Israel. Refuah Vet 18:168, 1961 31. Office International des Epizooties: African horse sickness in Spain. Disease Information 1:37, 4 Nov, 1988 32. Office International des Epizooties: African horse sickness in Spain. Disease Information 2:99, 18 Aug, 1989 33. Office International des Epizooties: African horse sickness in Portugal. Disease Information 2:128, 29 Sept, 1989 34. Office International des Epizooties: African horse sickness in Morocco. Disease Information 2:128,13 Oct, 1989 35. Office International des Epizooties: African horse sickness in Spain. Disease Information 3:115,26 Oct, 1990 36. Office International des Epizooties: African horse sickness in Morocco. Disease Information 3:113, 26 Oct, 1990 37. Office International des Epizooties: African horse sickness. 3:1-8,1991 38. Oellermann RA, Els HI, Erasmus BJ: Characterization of African horsesickness virus. Archives fur die Gesamte Virusforschung 29:163,1970 39. Ozawa Y, Nakata G, Shad-del F, et al: Transmission of African horse-sickness by a species of mosquito, Aedes aegypti Linnaeus. Am J Vet Res 27:695, 1966 40. Ozawa Y, Nakata G: Experimental transmission of African horsesickness by means of mosquitoes. Am J Vet Res 26:744, 1965 41. Ozawa Y: Bluetongue and related orbiviruses: Overview of the world situation. In Bluetongue and Related Orbiviruses. New York, Alan R. Liss, 1985, P 13 42. Pavri KM, Anderson CR: Isolation of a vaccine strain of African horse sickness virus from brains of two horses given polyvalent vaccine. Ind J Vet Sci 33:215, 1963 43. Reid NR: African horse sickness. Br Vet J 118:137, 1961 44. Salama SA, Dardiri AH, Awad Fl, et al: Isolation and identification of African horse sickness virus from naturally infected dogs in Upper Egypt. Can J Comp Med 45:392, 1981 45. Sellers RF: Weather, host and vector: Their interplay in the spread of insect-borne animal virus diseases. J Hyg 85:65,1980 46. Sellers RF, Pedgley DE, Tucker MR: Possible spread of African horse sickness on the wind. J Hyg 79:279,1977 47. Shah KV, Chinoy ON, Gokhale TB: Investigation of African horse sickness in India. II. Reaction in non-immune horses after vaccination with the polyvalent African horse sickness vaccine. Ind J Vet Sci 34:75, 1964 48. Swanepoel R, Erasmus BJ, Williams R, et al: Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers. Part 3. Virological and serological investigations. S Afr Med J 81:158, 1992 49. Theiler A: The susceptibility of the dog to African horsesickness. J Comp Pathol Ther 23:315, 1910 50. Theiler A: African horsesickness (Pestis equorum). S Afr Dep Agric Sci Bull 19, 1921 51. United States Department of Agriculture: African Horse Sickness Emergency Disease Guidelines. Hyattsville, MD, United States Department of Agriculture, Animal and Plant Health Inspection Service, Revised 1991 52. Van Rensburg IBJ, De Clerk I, Groenewald HB, et al: An outbreak of African horsesickness in dogs. J S Afr Vet Assoc 52:323, 1981
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53. Wetzel H, Nevill EM, Erasmus BJ: Studies of the transmission of African horsesickness. Onderstepoort J Vet Res 37:165, 1970
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James A. House, DVM, PhD U.s. Department of Agriculture Animal and Plant Health Inspection Service Foreign Animal Disease Diagnostic Laboratory Box 848 Greenport, NY 11944
0749-0739/93 $0.00 + .20
AFRICAN HORSE SICKNESS James A. House, DVM, PhD
African horse sickness (AHS) is a peracute, acute, subacute, or mild (horsesickness fever) disease of Equidae that causes mortality by inducing pathologic changes in the circulatory and respiratory systems. African horse sickness viruses (AH5V), of which there are nine serotypes, are biologically transmitted in nature by Culicoides spp and, perhaps, by mosquitoes.
HISTORICAL ASPECTS
AHS was first described by Theiler50 in 1921, when he related seven major epizootics of AHS in the Cape Province of South Africa between 1780 and 1918. The disease is endemic in sub-Saharan Africa; it occurs annually or seasonally wherever susceptible Equidae are present. 50 On numerous occasions, AHS has spread outside of its usual sub-Saharan African niche. In 1944, AHS serotype 3 spread from Egypt to Palestine, Syria, and Jordan.2 The most extensive epizootic, which was caused by serotype 9, occurred during 1959 to 1960. The disease occurred in Iran, West Pakistan, and Afghanistan in the summer of 1959. The virus apparently over-wintered and spread to Jordan, India, Turkey, Cyprus, Iraq, Syria, and Lebanon in 1960. It is estimated that 300,000 Equidae died or were destroyed during this epizootic. 20 ,'3 Another epizootic of AHS, caused by serotype 9, occurred in Algeria, Morocco, Tunisia, and Spain during 1965 to 1966?' 28 Local outbreaks of AHS, whose serotype has not been determined, have been reported in Pakistan (1974), Saudi Arabia (1975), and Yemen (1980-1991),41 In 1989, AHS (serotype 9) was reported in Saudi Arabia,1 The most recent outbreaks of AHS outside of sub-Saharan Africa were in Spain from 1987 to 1990,>1,31,32,35 Portugal in 1989,33 and Morocco in 1989 to 1990,34,36 The disease has not occurred in Spain or Portugal in 1991 or 1992,
From the United States Department of Agriculture, Animal and Plant Health Inspection Service, National Veterinary Service Laboratories, Veterinary Services, Foreign Animal Disease Diagnostic Laboratory, Greenport, New York
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VIRAL CHARACTERISTICS
AHS was shown to be caused by a filterable agent in 1900 by M'Fadyean.22 AHS is caused by viruses in the family Reoviridae, the genus Orbivirus, the subgroup AHSV, of which there are nine serotypes. 20. 26 The orbiviruses contain 10 segments of double-stranded RNA surrounded by two layers of viral cap someres.24 The AHSV is destroyed by heating to 70°C for 5 minutes, or to 50°C for 10 minutes.'8 The virus is rapidly inactivated by pH below 6.0. 3 These viruses are quite stable in blood when stored with various preservatives at refrigeration temperature. Other orbiviruses of veterinary importance are bluetongue, epizootic hemorrhagic disease, equine encephalosis, and Chuzan viruses.
EPIDEMIOLOGY Geographic Distribution
AHS has spread from its normal and current enzootic areas in sub-Saharan Africa on numerous occasions. The disease has been reported to occur sporadically in Pakistan (1974), Saudi Arabia (1975), and Yemen (1980-1981).4 1 It was reported in Saudi Arabia in 1989 ' and in Morocco in 198934 and 1990. 36 Thus, the Middle East is considered an active AHS area. Following the epizootics in Spain from 1987 through 1990, clinical cases have not been reported, but Spain has not been declared free of AHS by the USDA or Office International des Epizooties (OlE) as of June 1992. With the rapid movement of Equidae throughout the world, there is the distinct possibility that Equidae could leave a country where AHS was present but not yet diagnosed and enter the United States. The quarantine for Equidae coming into the United States from countries free of AHS is 5 to 7 days. This is within the incubation period of AHS, and such animals could legitimately pass through quarantine and into the mainland.
Transmission
African horse sickness is not a contagious disease; rather, it is arthropodborne and may spread to new areas via infected animals or vector movement. The principal vectors of AHS are Culicoides spp. Culicoides live in varied aquatic habitats, decaying vegetation or manure, low-lying areas, river basins and deltas, coastal areas, or swamps. Culicoides spend the vast majority of their life in the egg, larval, and pupal stages and overwinter this way. They feed from dusk to dawn, with the peak feeding times at twilight. Culicoides may generate several generations during a season, and the adult stages are normally present in the spring and summer with peak activity during the fall. Culicoides prefer not to enter buildings, and housing Equidae in barns diminishes the risk of their being bitten. DuToit' 2 detected AHSV in wild-caught Culicoides spp by inoculating a susceptible horse with a suspension of the insects. Further, he reported that he had experimentally transmitted AHSV using wild-caught culicoides. He fed Culicoides spp on an AHSV-infected horse, then fed it 12 days later on a susceptible horse that subsequently developed AHS.53 The vector competence of C. variipennis was substantiated in the laboratory by feeding gnats on infected embryonating
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chicken eggs and 1 week later refeeding the gnats on uninfected embryonating chicken eggs. 6 In Spain, ASHV-4 was isolated from pools of C. imicola and, for the first time, from pools of C. pulicaris and C. obsoletus with C. cataneii and C. lailae present as minority populations. It is of interest that "the range of both C. pulicaris and C. obsoletus probably extends much farther north and indeed these two species are probably the commonest midges in Northern Europe and the United Kingdom. 27 In endemic areas of Africa, the overwintering mechanism of the AHSV has not been clarified. Transovarial transmission of AHSV in culicoides has not been demonstrated. Possible means of viral survival suggested are that a yet-to-be determined reservoir host of AHSV may exist, or perhaps transovarial viral transmission may occur in unknown species of culicoides. Regarding overwintering, C. imicola has been found to survive "on the wing" the whole year in certain areas of Spain, providing a plausible mechanism for viral survival year to year. 27 Although culicoides are considered to be the major biological vector of AHSV, three species of mosquitoes have experimentally transmitted AHSV. 39,40 AHSV has been isolated from a camel tick, Hyalomma dromedarii, with the virus replicating through the developmental stages of this tick. 4 AHSV has been isolated from street dogs in Egypt.. Rhipicephalus sanguineus has been reported to transmit AHSV from sick dogs ·to susceptible dogs and horses, and from sick horses to susceptible dogs. Transovarial transmission of AHSV was not observed, but transtadial persistence of the virus from larva through the adult was reported. 9 Oral infection of dogs by ingestion of meat from AHSV-infected Equidae has been reported to cause mortality.5. 23. 49. 52 AHS may spread by insect movement. Evidence has been presented indicating that culicoides were carried 5 to 6 km46 and 40 to 700 km"s Although insects play the major role in transmission of AHSV, mechanical means such as by the use of contaminated surgical instruments and needles should be considered. Host Range
The natural host of AHS is Equidae. Dogs may become infected and suffer mortality by ingesting meat from AHSV-infected horses. s, 23. 49, 52 Camels have been reported to be infected with AHSV ..· 44 Among Equidae, horses are more susceptible than mules, which are more susceptible than donkeys, whereas zebras are the most resistant and show only minimal clinical signs. Naturally resistant horses may exist in north Africa and just south of the western Sahara.s Ancestors of these horses have been in the area since 2000 B.C. These animals were not vaccinated but had antibodies to AHSV without demonstrating any clinical sign of AHS.25 The African donkey is more resistant than donkeys in the Middle East, which suffered significant mortality in the 1944 epizootic.> Zebras are highly resistant to AHSV infection, and mortality is usually low.'" 16 CLINICAL ASPECTS Clinical Signs
AHS classically presents four clinical syndromes:'" 29, 50 the pulmonary or peracute form; the cardiac or subacute form; the mixed or acute form (presenting signs of the pulmonary and cardiac forms); and the horse sickness fever form.
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The peracute or pulmonary form has an incubation of 3 to 5 days and runs the shortest course, with animals presenting clinical signs for 1 to 3 days. The first clinical sign is fever (103°-105°P; 39S-40SC), followed by congestion of the mucous membranes of the eyes, nose, and mouth. Usually, within a few hours prior to death, animals become depressed and may have an increased respiratory rate (up to 60 or more per minute), profuse sweating, and spasmodic cough. During the terminal stage, frothy fluid (which may be blood-tinged) may exude from the nostrils. Auscultation may reveal lung edema and hydrothorax, as evidenced by moist rales and muffled heart sounds. Equidae may die peracutely without presenting significant clinical or pathologic changes. Mortality is about 95%. The subacute, edematous, or cardiac form has an incubation from 7 to 14 days, with the course of the disease lasting 3 to 6 days. The first sign is fever (101°105°P; 3SS-40'soC) followed by congestion of the mucous membranes of the eyes, nose, and mouth. Late in the clinical course, subcutaneous edema and edema in intermuscular fascia swellings may occur in the neck, jugular furrow, extensor muscles of thoracic and lumbar regions, and hip. Edema of the supraorbital fossa, which may cause it to bulge, is considered pathognomonic for the cardiac form. lO The eyelids and intermandibular space may develop edema. Animals usually continue to eat and drink throughout the course of the disease, although depression may occur toward the end of the syndrome. Petechial hemorrhages may occur on the ventral surface of the tongue and in the conjunctiva. Signs of colic are not uncommon. Death usually occurs 4 to 8 days after the onset of fever. Mortality is generally 50% in the cardiac form. The acute or mixed form has an incubation period of 5 to 7 days. This is the most common form of AHS and presents clinical signs of both the pulmonary and cardiac forms. Mortality ranges from 50% to 95%, and death usually occurs 3 to 6 days after the onset of fever. The horse sickness fever form is not commonly detected since it is a mild form of the disease; it is purported to occur in "partially immune" animals in endemic areas and resistant species such as the donkey and zebra. The incubation period ranges from 5 to 14 days. A low-grade fever (101°-103°P; 3SS-39'soC) may be detected, especially in the afternoon, for a period of 5 to S days. The conjunctiva may be congested, and there may be a slight anorexia and depression. Animals affected with the horse sickness fever form recover. The most consistent signs common to all the forms of AHS are fever and congestion of the ocular, nasal, and oral mucous membranes. The distribution of clinical signs for the different forms of AHS is compared in Table 1.
Pathology
The gross pathology of the various forms of AHS has been well-described.!4, In the necropsy of Equidae in which clinical and epidemiologic signs suggest AHS, the first procedure is to reflect the skin from the thorax, neck, and head to examine for subcutaneous edema. Next, carefully dissect the muscle bundles and fascia, looking for intermuscular fascial edema in the neck, extensor muscles of thoracic and lumbar regions, and intercostal areas. The area adjacent to the ligamentum nuchae and jugular furrows are sites of predilection for edema caused by AHSV infection. Pathologic changes observed in the pulmonary form include severe lung edema and hydrothorax, with several liters of straw-colored fluid present in the thorax. Lung edema is present when the interlobular septae are grossly visible 29, 50
AFRICAN HORSE SICKNESS
Table 1. POSSIBLE CLINICAL SIGNS AFRICAN HORSE SICKNESS
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IN THE DIFFERENT FORMS OF Form of the Disease
Clinical sign Nonpurulent conjunctivitis Fever Congested nasal and oral mucous membranes Increased respiratory rate Moist rales Muffled heart sounds Edema of the neck Edema of the supraorbital fossa Colic
Pulmonary Yes Yes Yes
Cardiac Yes Yes Yes
Mixed Yes Yes Yes
Horse Fever Yes Yes Yes
Yes Yes Yes No No No
Yes Yes Yes Yes Yes Yes
Yes Yes Yes Yes Yes Yes
Rare No No No No No
and the pleura presents a glassy appearance (subpleural edema). There may be petechial hemorrhages on the lungs and periaortic edema. Lymph nodes of the thoracic and abdominal cavities may be edematous. The gland~lar portion of the stomach may be congested, and there may be petechiae in the serosae of the intestines. In the cardiac form, edema may occur in the subcutaneous tissues of the thorax, neck, intermuscular areas of the neck, intercostal muscles, extensor muscles of thoracic and lumbar regions, deep muscles of the hip, and lymph nodes. Hydropericardium is observed with up to 2 L or more of straw-colored fluid present. There may be petechial and ecchymotic hemorrhages in the epicardium and endocardium; the significance of these is controversial. Hemorrhages may be observed in the papillary muscles near the junction with the chordae tendineae. The lungs may be slightly heavier than normal. There may be petechial hemorrhages in the serosa of the intestines. The pathologic changes in the mixed form of AHS are a combination of those described for the pulmonary and cardiac forms, but usually there are more significant pathologic changes in the lungs or extensive edema, indicating predominance of either the pulmonary or cardiac form, respectively. Microscopic changes in the lungs include edema fluid containing fibrin and inflammatory cells suggestive of an exudative pneumonia.>9 There is depletion of lymphoid cells and necrosis of germinal centers in the spleen and lymph nodes. Centrilobular congestion of the liver lobules with hydropic degeneration of hepatocytes is commonly observed.
DIAGNOSIS AND PROGNOSIS
A disease of Equidae causing high mortality, lung edema, subcutaneous and intermuscular edema, occurring during the time of year when culicoides are active (spring, summer, but mainly autumn) should evoke a presumptive diagnosis of AHS. Some regard edema of the supraorbital fossae as pathognomonic for the cardiac form of AHS.1O When AHS is suspected, contact the state or Federal veterinary officials immediately. They will arrange for a foreign animal disease diagnostician to visit the premises, examine the animals, gather epidemiologic information, necropsy animals, advise on quarantines, and send samples to the USDA's Foreign Animal
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Disease Diagnostic Laboratory (FADDL) at Plum Island, New York. The FADDL is the only diagnostic laboratory in the United States that is allowed to work with AHSV; all AHS diagnostic tests are performed there. Differential diagnoses include equine infectious anemia, equine viral arteritis, equine piroplasmosis (babesiosis), equine influenza, purpura hemorrhagica, equine rhinopneumonitis, ingestion of poisonous plants such as Crotalaria, and colic. Virus isolation via the intracranial inoculation of suckling mice 1 to 3 days of age, inoculation of BHK-21 or Vero cells, and intravenous inoculation of 10- to 12-day embryonating chicken eggs (ECE) are used for the isolation of AHSV. Virus is identified by group reactive tests such as complement fixation, indirect fluorescent antibody, or enzyme-linked immunosorbent assay (ELISA) . The specific serotype is identified by virus neutralization using serotype-specific serums. Serologically, group reactive antibody (reacting against all nine serotypes) can be detected by the agar gel immunodiffusion, indirect fluorescent antibody, complement fixation, and ELISA. Type specific antibody is measured by VN. ' 8 There is no specific treatment for AHS. Mortality varies from 50% to over 95%. The highest mortality occurs in the peracute pulmonary form. In endemic areas "natural resistance," especially in donkeys and zebras, and vaccination may ameliorate or prevent the disease.
PREVENTION AND CONTROL
The philosophy for the control of AHS differs for endemic areas, where unknown reservoirs of the AHSV may exist, and nonendemic areas. In a nonendemic area, the goal is to eradicate the disease, whereas in an endemic area, the main thrust of regulatory efforts is directed at preventing losses from the disease. In the United States "The goal of disease prevention and control is to contain ASH in as small a geographic area as pOSSible, and rapidly and efficiently eradicate it from the United States. Expanse of affected areas will depend on timeliness of virus detection, distribution and population density of the insect vectors, and movement of equines. Early detection of the virus combined with prompt initiation of quarantine and vector control are critical to limiting the spread and permitting disease eradication."s1 Other actions include "Take immediate action after detection of AHS virus to eliminate contact between susceptible animals and known insect vectors. Destroy and properly dispose of, or place in Culicoidesproof enclosures, all diseased animals. Prohibit movement of susceptible animals from the affected premises and the areas of possible infected vector activity by issuance of quarantines and taking required enforcement actions."s1 There would be significant discourse with representatives of the equine industry concerning the outbreak. In the United States, an emergency disease declaration would be made, an emergency disease eradication network (Regional Emergency Animal Disease Eradication Organization "READEO") would be called into action, all movements of Equidae would be traced back, and vaccination would be initiated if the former actions did not control and eradicate the disease. To keep diagnostic preparedness at peak, the USDA has a cadre of about 300 foreign animal disease diagnosticians active to assist in diagnosis, epidemiologic examinations, and sampling of suspect cases of AHS. These diagnosticians are veterinarians trained in field diagnosis at the FADDL during annual foreign animal disease training courses where 14 foreign animal diseases, including AHS, are demonstrated in their natural hosts.
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In AHS endemic areas of Africa, vaccines have been developed and used successfully to control losses from AHS. The first vaccines were modified live vaccines (ML V) of high adult mouse brain passage. 3 These neurotropic vaccines were, in many cases, effective for the prevention of clinical disease and death, but some of the vaccines against certain serotypes were not effective,!9 and others had the potential to produce encephalitis in horses and donkeys.30. 4 2, 47 Erasmus13 showed that these vaccines caused encephalitis in guinea pigs when administered intranasally. Cell-culture ML V vaccines were developed that were reported to be efficacious; no safety problem was described. ls These cell-culture vaccines are now in use in South Africa and were used in Spain in 1987 to 1990. The cell culture MLV against serotype 4 of AHS did not produce a detectible viremia in vaccinated Equidae, and it did protect against clinical disease in vaccinates that were challenge-inoculated with virulent AHSV-4. A potential weakness of these vaccines is that they may not prevent viremia in vaccinates that are exposed to virulent AHSV. One of three vaccinates challenge-inoculated with virulent AHSV-4 had a viremia (10 2 1 to 104 8 infectious particies/mL of blood between 3 to 11 days after challenge inoculation) quite similar to that found in nonimmune animals. A second pony had a viremia of 102.8 infectious particies/mL of blood. This was likely residual challenge virus. The third vaccinate had no detectible viremia following challenge inoculation.17 A commercial inactivated AHS vaccine was recently developed (Dubourget P, Preaud JM, Detraz N, et al: Development, production and quality control of an industrial inactivated vaccine against AHS type IV. Submitted for publication, 1991). One dose prevented death of nine of nine vaccinates and prevented clinical signs in six of nine vaccinates. A viremia between 1026 and 103.1 infectious AHSV particies/mL of blood occurred for 3 days in one of nine vaccinates. All three control ponies died following challenge inoculation and had viremias > 10s0 infectious AHSV particies/mL of blood (House JA, Lombard M, House C, et al: Efficacy of an inactivated vaccine for African horse sickness serotype 4. Submitted for publication, 1991). A significant problem in evaluating the efficacy of vaccines for use in eradicating AHSV is that the threshold level of viremia that would allow the culicoides vector to become infected is unknown. Studies are currently underway at the FADDL to determine this. There are no reports of humans becoming infected with AHSV of field origin. Certain strains of neurotropic AHSV may cause encephalitis and chorioretinitis following intranasal exposure of humans to the virus. 48
SUMMARY
AHS is a noncontagious vector-borne disease of Equidae caused by Orbiviruses. Species susceptibility in decreasing order is horses, mules, donkeys, and zebras. The main vectors of AHS are culicoides. The disease is endemic in subSaharan Africa, but epizootics have occurred outside of this area on several occasions. The most recent outbreaks outside of the endemic area were in Spain, Morocco, and Portugal between 1987 and 1990. AHS causes mortality up to 95% and is classically divided into four clinical forms: the pulmonary, cardiac, mixed, and horse fever forms. Pathologic changes are subcutaneous and intermuscular edema and lung edema. The most consistent clinical signs include fever, nonpurulent conjunctivitis, and increased respiratory rate. Prevention and control measures include quarantines, control of insects, and vaccination. There is no treat-
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ment for AHS. Neurotropic strains of AHSV may cause retinitis and encephalitis in humans. References 1. Anderson EC, Mellor P, Hamblin C: African horse sickness in Saudi Arabia. Vet Rec 125:489, 1989 2. Alexander RA: The 1944 epizootic of horse sickness in the Middle East. Onderstepoort J Vet Res 53:471, 1948 3. Alexander RA, Dutoit PJ: The immunization of horses and mules against horse sickness by means of neurotropic virus of mice and guinea pigs. Onderstepoort J Vet Res 2:375, 1934 4. Awad FI, Amin MM, Salama SA, et al: The role played by Hyalomma dromedarii in the transmission of African horse sickness virus in Egypt. Bull Anim Health Prod Afr 29:337,1981 5. Bevan LEW: The transmission of African horse-sickness to the dog by feeding. Vet J 67:402,1911 6. Boorman J, Mellor P A, Penn M, et al: The growth of African horse-sickness virus in embryonated hen eggs and the transmission of virus by Culicoides variipennis Coquillet (Diptera, Ceratopogonidae). Arch ViroI47:343, 1975 7. Botija CS, Ordas A, Ovejero JA, et al: El Diagnostico de la peste equina en Espana. Bulletin Office International des Epizooties 68:695, 1967 8. Bourdin P: Ecology of African horsesickness. In Proceedings of the Third International Conference on Equine Infectious Diseases. Basel, S. Karger, 1973 p 12 9. Dardiri AH, Salama SA: African horsesickness: An overview. Equine Vet Sci 8:46-49, 1988 10. Dardiri AH: African horse sickness. Foreign animal diseases; their prevention diagnosis and control [Revised] . Richmond, VA, Committee on Foreign Animal Diseases of the United States Animal Health Association, 1984, p 23 11. Davies FG, Otieno S: Elephants and zebras as possible reservoir hosts for African horsesickness virus. Vet Rec 100:291, 1977 12. DuToit RM: The transmission of blue-tongue and horse-sickness by Culicoides. Onderstepoort J Vet Sci Anim Ind 19:7, 1944 13. Erasmus BJ: Preliminary observations on the value of the guinea-pig in determining the innocuity and antigenicity of neurotropic attenuated horsesickness strains. Onderstepoort J Vet Res 30:11, 1963 14. Erasmus BJ: The pathogenesis of African horsesickness. In Proceedings of the Third International Conference on Equine Infectious Diseases. Basel, S. Karger, 1973, p 1 15. Erasmus BJ: A new approach to polyvalent immunization against African horsesickness. In Proceedings of the Fourth International Conference on Equine Infectious Diseases. Lyon, Veterinary Publications, 1976, p 401 16. Erasmus BJ, Young E, Pieterse LM, et al: The susceptibility of zebra and elephants to African horsesickness virus. In Proc Fourth Int Conf Equine Infect Dis, Lyon, Veterinary Publications, 1976, p 409 17. House C, House JA, Mebus CA: A Review of African Horse Sickness with emphasis on selected vaccines. Tropical Veterinary Medicine: Current Issues and Perspectives. Ann NY Acad Sci 653:228,1992 18. House C, Mikiciuk PE, Berninger ML: Laboratory diagnosis of African horse sickness: Comparison of serological techniques and evaluation of storage methods of samples for virus isolation. J Vet Diagn Invest 2:44,1990 19. House JA, House C: Immunization studies on African horse sickness. In Proceedings of the 93rd Annual Meeting of the United States Animal Health Association, Las Vegas, 1989, p 356 20. Howell PG: The isolation and identification of further antigenic types of African horsesickness virus. Onderstepoort J Vet Res 29:139, 1962 21. Lubroth J: African horse sickness and the epizootic in Spain, 1987. Proc AAEP 33:871, 1988 22. M'Fadyean J: African horsesickness. J Comp Pathol Ther 13:1, 1900
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23. M'Fadyean J: The susceptibility of the dog to African horse-sickness. J Comp Pathol Ther 23:27, 1910 24. Matthews REF: Classification and nomenclature of viruses. Intervirology 17:1, 1982 25. Maurice Y, Provost A: La peste equine a type 9 en Afrique central. Enquete serologique. Rev Elev Med Vet Pays Trop 20:21, 1967 26. McIntosh BM: Immunological types of horsesickness virus and their significance in immunization. Onderstepoort J Vet Res 27:465, 1958 27. Mellor PS, Boned J, Hamblin C, et al: Isolations of African horse sickness virus from vector insects made during the 1988 epizootic in Spain. Epidemiol Infect 105:447, 1990 28. Montilla DR, Marti P: Epizootologia de la peste equina en Espana. Bulletin Office International des Epizooties 68:705, 1967 29. Newsholme SJ: A morphological study of the lesions of African horsesickness. Onderstepoort J Vet Res 50:7, 1983 30. Nobel TR, Neumann F: Vaccination against African horse sickness and post-vaccination reaction in Israel. Refuah Vet 18:168, 1961 31. Office International des Epizooties: African horse sickness in Spain. Disease Information 1:37, 4 Nov, 1988 32. Office International des Epizooties: African horse sickness in Spain. Disease Information 2:99, 18 Aug, 1989 33. Office International des Epizooties: African horse sickness in Portugal. Disease Information 2:128, 29 Sept, 1989 34. Office International des Epizooties: African horse sickness in Morocco. Disease Information 2:128,13 Oct, 1989 35. Office International des Epizooties: African horse sickness in Spain. Disease Information 3:115,26 Oct, 1990 36. Office International des Epizooties: African horse sickness in Morocco. Disease Information 3:113, 26 Oct, 1990 37. Office International des Epizooties: African horse sickness. 3:1-8,1991 38. Oellermann RA, Els HI, Erasmus BJ: Characterization of African horsesickness virus. Archives fur die Gesamte Virusforschung 29:163,1970 39. Ozawa Y, Nakata G, Shad-del F, et al: Transmission of African horse-sickness by a species of mosquito, Aedes aegypti Linnaeus. Am J Vet Res 27:695, 1966 40. Ozawa Y, Nakata G: Experimental transmission of African horsesickness by means of mosquitoes. Am J Vet Res 26:744, 1965 41. Ozawa Y: Bluetongue and related orbiviruses: Overview of the world situation. In Bluetongue and Related Orbiviruses. New York, Alan R. Liss, 1985, P 13 42. Pavri KM, Anderson CR: Isolation of a vaccine strain of African horse sickness virus from brains of two horses given polyvalent vaccine. Ind J Vet Sci 33:215, 1963 43. Reid NR: African horse sickness. Br Vet J 118:137, 1961 44. Salama SA, Dardiri AH, Awad Fl, et al: Isolation and identification of African horse sickness virus from naturally infected dogs in Upper Egypt. Can J Comp Med 45:392, 1981 45. Sellers RF: Weather, host and vector: Their interplay in the spread of insect-borne animal virus diseases. J Hyg 85:65,1980 46. Sellers RF, Pedgley DE, Tucker MR: Possible spread of African horse sickness on the wind. J Hyg 79:279,1977 47. Shah KV, Chinoy ON, Gokhale TB: Investigation of African horse sickness in India. II. Reaction in non-immune horses after vaccination with the polyvalent African horse sickness vaccine. Ind J Vet Sci 34:75, 1964 48. Swanepoel R, Erasmus BJ, Williams R, et al: Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers. Part 3. Virological and serological investigations. S Afr Med J 81:158, 1992 49. Theiler A: The susceptibility of the dog to African horsesickness. J Comp Pathol Ther 23:315, 1910 50. Theiler A: African horsesickness (Pestis equorum). S Afr Dep Agric Sci Bull 19, 1921 51. United States Department of Agriculture: African Horse Sickness Emergency Disease Guidelines. Hyattsville, MD, United States Department of Agriculture, Animal and Plant Health Inspection Service, Revised 1991 52. Van Rensburg IBJ, De Clerk I, Groenewald HB, et al: An outbreak of African horsesickness in dogs. J S Afr Vet Assoc 52:323, 1981
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53. Wetzel H, Nevill EM, Erasmus BJ: Studies of the transmission of African horsesickness. Onderstepoort J Vet Res 37:165, 1970
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James A. House, DVM, PhD U.s. Department of Agriculture Animal and Plant Health Inspection Service Foreign Animal Disease Diagnostic Laboratory Box 848 Greenport, NY 11944