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GETAH VIRUS INFECTION T. S. Mair* and P. J. Timoney† Bell Equine Veterinary Clinic, Mereworth, Maidstone, Kent ME18 5GS; and †Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546-0099, USA. Keywords: horse; Getah virus; ; Semliki Forest

Summary is classified in the Semliki Forest complex along with Getah virus is an arbovirus that was first isolated Semliki Forest, Bebaru, Ross River, Chikungunya, from mosquitoes in Malaysia in 1955. Outbreaks of O’nyong-nyong, Una and Mayaro viruses (van infection by Getah virus have been recorded in horses Regenmortel et al. 2000). Several subtypes of Getah in Japan and India. Infection can occur in a wide range virus are recognised, including Sagiyama, Ross River of vertebrates, and the virus is probably maintained and Bebaru viruses (Calisher and Walton 1996). in a mosquito-pig-mosquito cycle. Clinical disease in Getah virus possesses haemagglutinating and horses is generally mild, characterised by pyrexia, complement fixing antigens, which have been used to oedema of the limbs, urticaria and a stiff gait. An develop diagnostic tests for the virus. These tests in inactivated whole-virus vaccine is available in Japan. addition to the neutralisation test have been used to investigate antigenic relationships between different Introduction strains and subtypes of virus (Fukunaga et al. 2000). Getah virus is an arbovirus that was first isolated from mosquitoes ( gelidus) in Malaysia in 1955 (Berge Epidemiology 1975). However, it was not until 1978 that the virus Getah virus is transmitted by mosquitoes, and is was shown to be responsible for a mild disease among widely distributed in southeast Australasia and racehorses in Japan (Kamada et al. 1980; Sentsui and surrounding countries, including Australia, Borneo, Kono 1980a; Timoney 2004). Subsequent outbreaks of Cambodia, China, Indonesia, Japan, Korea, Getah virus infection have been documented in Malaysia, Mongolia, the Philippines, Russia, racehorses in Japan in the 1970s and 1980s (Sentsui Thailand, Sarawak, Siberia, Sri Lanka and Vietnam and Kono 1985) and among breeding horses in India (Calisher and Walton 1996; Fukunaga et al. 2000; in 1990 (Brown and Timoney 1998). Infection with the Timoney 2004). Natural infection in wildlife is virus also occurs in other domestic animals, including believed to be subclinical (Fukunaga et al. 2000). In pigs where it has been associated with illness and tropical areas of Asia, pigs appear to be important in death in young piglets aged up to 18 days. Serological maintaining a reservoir of infection via a mosquito- evidence of infection has been found in a large number pig-mosquito cycle (Chanas et al. 1977). Pigs, and of vertebrate species (mammals, birds and reptiles) in possibly other vertebrates, may play an important which the infection appears to be subclinical (Doherty role as amplifying hosts for the virus (Fukunaga et al. 1966). There is no evidence that the virus can et al. 2000). infect man (Fukunaga et al. 2000). Serological surveys of horses in Japan have shown that the virus is widespread in this country, with Aetiology seropositive rates up to 93% (Imagawa et al. 1981; Sentsui and Kono 1980b; Brown and Timoney 1998; Getah virus is a positive-stranded RNA virus Sugiura and Shimada 1999). The highest rates of belonging to the genus of the family seropositivity occurred in older horses in the cooler Togaviridae (Calisher et al. 1980; Timoney 2004). It regions of northern Japan. Seroprevalence was reported as 17% in India and 25% in Hong Kong *Author to whom correspondence should be addressed. (Kamada et al. 1991; Shortridge et al. 1994). Many EVE Man 08-047 Mair v2:Layout 1 14/08/2009 11:28 Page 156

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cases of Getah virus infection in horses are subclinical Clinical signs (Fukunaga et al. 2000). Clinical infection caused by Getah virus has been The principal vectors for the transmission of observed almost exclusively in the horse. Outbreaks Getah virus to horses are mosquitoes (species of Culex of the disease in horses have been sporadic, and have or ) (Calisher and Walton 1996; Fukunaga not been associated with any mortality (Fukunaga et al. 2000), although horse to horse transmission et al. 2000). The morbidity rate in one outbreak of could also occur (Sentsui and Kono 1980a). High infection in racehorses was 38% (Kamada et al. 1980; levels of virus can be found in nasal secretions of Sentsui and Kono 1980a), with slow and irregular horses experimentally infected by Getah virus by the spread of infection. nasal route (Kamada et al. 1991), thereby permitting The clinical signs associated with Getah virus horse to horse spread in animals in close contact. infection in horses vary depending on the strain of virus and viral dose (Timoney 2004). Some infections Nonvector spread of the virus was believed to have only produce a febrile response with associated contributed to the outbreak of Getah virus in India in inappetence and depression (Sentsui and Kono 1990 (Brown and Timoney 1998). 1980a). The febrile stage lasts 1–4 days. Other signs seen in infected horses include lower limb oedema (Fig 1), swelling of the submandibular lymph nodes (Fig 2), urticaria (especially on the neck, shoulders and hind quarters) (Fig 3) and a stiff gait (Kamada et al. 1980; Sentsui and Kono 1980a; Fukunaga et al. 1981a; Brown and Timoney 1998). Mild colic, icterus and scrotal oedema have also been reported (Timoney 2004). Limb oedema and urticaria usually appear several days after the onset of pyrexia. Mild anaemia and a transient lymphopenia may be present (Fukunaga et al. 2000). Serum alkaline phosphatase can be elevated during the acute phase of the infection, whereas serum lactic dehydrogenase and glutamine pyruvic transaminase rise during FIGURE 1: Lower limb oedema due to Getah virus infection. convalescence (Calisher and Walton 1996). Most affected horses make a full clinical recovery within one week, although a small number may require up to 2 weeks to recover (Timoney 2004). Abortion is not a feature of the disease, and foals born to mares that

FIGURE 2: Submandibular lymphadenopathy associated with Getah virus infection. FIGURE 3: Urticaria due to Getah virus infection. EVE Man 08-047 Mair v2:Layout 1 14/08/2009 11:28 Page 157

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have had the disease during gestation are normal horses to virus-infected mosquitoes can be reduced by (Brown and Timoney 1998). In experimental housing them during dusk and at night. infections, the clinical signs are similar, but infected An inactivated whole-virus vaccine is available in horses also commonly develop a serous nasal Japan. Horses receive an annual booster dose of the discharge (Kamada et al. 1991). vaccine in May or June, prior to the onset of the mosquito season. No epidemics of Getah virus Diagnosis infection have been recorded in horses in Japan since In view of its clinical similarity to a range of other the current vaccination programme was implemented infectious and noninfectious equine diseases, a in 1979 (Timoney 2004). provisional clinical diagnosis must be confirmed through laboratory examination. Included in a References differential diagnosis of Getah virus infection are Berge, T.O. (1975) International catalogue of , including certain other viruses of vertebrates. In: DHEW Publication No equine viral arteritis, equine rhinopneumonitis, (CDC) 78-8301. US Department of Health, Education and equine encephalosis, equine influenza, equine Welfare, Public Health Service, Washington DC. p 278. infectious anaemia, African horse sickness fever, Brown, C.M. and Timoney, P.J. (1998) Getah virus infection in purpura haemorrhagica and hoary alyssum toxicosis. Indian horses. Trop. Anim. Hlth. Prod. 30, 241-252. Virus isolation or demonstration of viral nucleic acid Calisher, C.H. and Walton, T.E. (1996) Getah virus infections. In: Virus Infections of Equines, Ed: M.K. Studdert, Elsevier, by reverse-transcription polymerase chain reaction Amsterdam. pp 157-165. may be performed on nasal swabs, unclotted blood or Calisher, C.H., Shope, R.E., Brandt, W., Casals, J., Karabatsos, N., saliva of acutely infected animals (Kamada et al. Murphy, F.A., Tesh, R.B. and Wiebe, M.E. (1980) Proposed 1980; Sentsui et al. 1980; Fukunaga et al. 1981a). The antigenic classification of registered arboviruses: Togavitidae, virus can be cultivated in a range of equine and alphavirus. Intervirol. 14, 229-232. nonequine cell culture systems, especially Vero and Chanas, A.C., Johnson, K.B. and Simpson, D.I.H. (1977) A comparative study of related – a naturally occurring RK-13 cell lines, as well as in suckling mice model of antigenic variation in the Getah sub-group. J. Gen. inoculated by the intracerebral route. Highest rates Virol. 35, 455-462. of virus isolation have been achieved from plasma Doherty, R.L., Gorman, B.M., Whitebread, R.H. and Carley, J.G. (Fukunaga et al. 1981b). Detection of Getah virus is (1966) Studies of arthropod-borne virus infections in Queensland: V. Survey of antibodies to Group A arboviruses in man and other optimal where specimens are collected as early as animals. J. expt. Biol. Sci. 44, 365-378. possible after the onset of fever. Fukunaga, Y., Kumanomido, T. and Kamada, M. (2000) Getah virus Serum antibodies to Getah virus can be detected as an equine pathogen. Vet. Clin. N. Am.: Equine Pract. 16, by haemagglutination inhibition, complement 605-617. fixation, enzyme-linked immunosorbent assay Fukunaga, Y., Ando, Y., Kamada, M., Imagawa, H., Wada, R., (ELISA) and neutralisation tests (Kamada et al. Kumanomido, T., Akiyama, Y., Watanabe, O., Niwa, K., Takenaga, S., Shibata, M. and Yamamoto, T. (1981a) An 1980; Sentsui and Kono 1980; Sentsui and Kono outbreak of Getah virus infection in horses – clinical and 1985; Brown and Timoney 1998). If possible, paired epizootological aspects at the Miho Training Center in 1978. samples taken during the acute and convalescent Bulletin of the Equine Research Institute 18, 94-102. stages of the disease should be assayed. The Fukunaga, Y., Kumanomido, T., Imagawa, H., Ando, Y., Kamada, M., Wada, R. and Akiyama, Y. (1981b) Isolation of picornavirus neutralisation test is considered the most specific from horses associated with Getah virus infection. Jap. J. vet. test at differentiating Getah virus infection from Sci. 43, 569-572. other antigenically related alphaviruses (Chanas Imagawa, H., Ando, Y., Kamada, M., Sugiura, T., Kumanomido, T., et al. 1977). Fukunaga, Y., Wada, R., Hirasawa, K. and Akiyama, Y. (1981) Sero-epizootogical survey of Getah virus infection in light horses in Japan. Jap. J. vet. Sci. 43, 797-802. Control Kamada, M., Ando, Y., Fukunaga, Y., Kumanomido, T., Imagawa, Control of Getah virus in endemic areas relies on H., Wada, R. and Akiyama, Y. (1980) Equine Getah virus control of the mosquito vector (Fukunaga et al. 2000; infection: Isolation of the virus from racehorses during a enzootic in Japan. Am. J. Trop. Med. Hyg. 29, 984-988. Timoney 2004). This can be achieved by eliminating Kamada, M., Kumanomido, T., Wada, R., Fukunaga, Y., Imagawa, or reducing mosquito breeding sites, and use of H. and Sugiura, T. (1991) Intranasal infection of Getah virus in larvicides and adulticides. The risk of exposure of experimental horses. J. vet. Med. Sci. 53, 855-858. EVE Man 08-047 Mair v2:Layout 1 14/08/2009 11:28 Page 158

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Sentsui, H. and Kono, Y. (1980a) An epidemic of Getah virus race tracks from 1991 to 1997 in Japan. J. vet. Med. Sci. 61, infection among racehorses: Isolation of the virus. Res. vet. Sci. 877-881. 29, 157-161. Timoney, P.J. (2004) Getah virus infection. In: Infectious Diseases of Sentsui, H. and Kono, Y. (1980b) Survey of antibody to Getah virus Livestock, 2nd edn., Eds: J.A.W. Coetzer and R.C. Tustin, Oxford in horses in Japan. Natl. Inst. anim. Health Q. 20, 39-43. University Press, Cape Town. pp 1023-1026. Sentsui, H. and Kono, Y. (1985) Reappearance of Getah virus infection among horses in Japan. Jap. J. vet. Sci. 47, 333-335. Van Regenmortel, M.H.V., Fauquet, C.M., Bishop, D.H.L., Carstens, Shortridge, K.F., Mason, D.K., Watkins, K.L. and Aaskov, J.G. (1994) E.B., Estes, M.K., Lemon, S.M., Maniloff, J., Mayo, M.A., Serological evidence for the transmission of Getah virus in Hong McGeoch, D.J., Pringle, C.R. and Wickner, R.B. (2000) Virus Kong. Vet. Rec. 134, 527-528. taxonomy: Classification and nomenclature of viruses. In: 7th Sugiura, T. and Shimada, K. (1999) Seroepizootological survey of Report of the International Committee on Taxonomy of Viruses, Japanese encephalitis virus and Getah virus in regional horse Academic Press, San Diego. pp 884-887.