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EVE Man 08-047 Mair v2:Layout 1 14/08/2009 11:28 Page 155 Getah virus infection 155 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; arbovirus; Semliki Forest viruses Summary Getah virus is an arbovirus that was first isolated from mosquitoes in Malaysia in 1955. Outbreaks of infection by Getah virus have been recorded in horses in Japan and India. Infection can occur in a wide range of vertebrates, and the virus is probably maintained in a mosquito-pig-mosquito cycle. Clinical disease in horses is generally mild, characterised by pyrexia, oedema of the limbs, urticaria and a stiff gait. An inactivated whole-virus vaccine is available in Japan. Introduction Getah virus is an arbovirus that was first isolated from mosquitoes (Culex gelidus) in Malaysia in 1955 (Berge 1975). However, it was not until 1978 that the virus was shown to be responsible for a mild disease among racehorses in Japan (Kamada et al. 1980; Sentsui and Kono 1980a; Timoney 2004). Subsequent outbreaks of Getah virus infection have been documented in racehorses in Japan in the 1970s and 1980s (Sentsui and Kono 1985) and among breeding horses in India in 1990 (Brown and Timoney 1998). Infection with the virus also occurs in other domestic animals, including pigs where it has been associated with illness and death in young piglets aged up to 18 days. Serological evidence of infection has been found in a large number of vertebrate species (mammals, birds and reptiles) in which the infection appears to be subclinical (Doherty et al. 1966). There is no evidence that the virus can infect man (Fukunaga et al. 2000). Aetiology Getah virus is a positive-stranded RNA virus belonging to the genus Alphavirus of the family Togaviridae (Calisher et al. 1980; Timoney 2004). It *Author to whom correspondence should be addressed. is classified in the Semliki Forest complex along with Semliki Forest, Bebaru, Ross River, Chikungunya, O’nyong-nyong, Una and Mayaro viruses (van Regenmortel et al. 2000). Several subtypes of Getah virus are recognised, including Sagiyama, Ross River and Bebaru viruses (Calisher and Walton 1996). Getah virus possesses haemagglutinating and complement fixing antigens, which have been used to develop diagnostic tests for the virus. These tests in addition to the neutralisation test have been used to investigate antigenic relationships between different strains and subtypes of virus (Fukunaga et al. 2000). Epidemiology Getah virus is transmitted by mosquitoes, and is widely distributed in southeast Australasia and surrounding countries, including Australia, Borneo, Cambodia, China, Indonesia, Japan, Korea, Malaysia, Mongolia, the Philippines, Russia, Thailand, Sarawak, Siberia, Sri Lanka and Vietnam (Calisher and Walton 1996; Fukunaga et al. 2000; Timoney 2004). Natural infection in wildlife is believed to be subclinical (Fukunaga et al. 2000). In tropical areas of Asia, pigs appear to be important in maintaining a reservoir of infection via a mosquitopig-mosquito cycle (Chanas et al. 1977). Pigs, and possibly other vertebrates, may play an important role as amplifying hosts for the virus (Fukunaga et al. 2000). Serological surveys of horses in Japan have shown that the virus is widespread in this country, with seropositive rates up to 93% (Imagawa et al. 1981; Sentsui and Kono 1980b; Brown and Timoney 1998; Sugiura and Shimada 1999). The highest rates of seropositivity occurred in older horses in the cooler regions of northern Japan. Seroprevalence was reported as 17% in India and 25% in Hong Kong (Kamada et al. 1991; Shortridge et al. 1994). Many EVE Man 08-047 Mair v2:Layout 1 14/08/2009 11:28 Page 156 156 cases of Getah virus infection in horses are subclinical (Fukunaga et al. 2000). The principal vectors for the transmission of Getah virus to horses are mosquitoes (species of Culex or Aedes) (Calisher and Walton 1996; Fukunaga et al. 2000), although horse to horse transmission could also occur (Sentsui and Kono 1980a). High levels of virus can be found in nasal secretions of horses experimentally infected by Getah virus by the nasal route (Kamada et al. 1991), thereby permitting horse to horse spread in animals in close contact. Nonvector spread of the virus was believed to have contributed to the outbreak of Getah virus in India in 1990 (Brown and Timoney 1998). FIGURE 1: Lower limb oedema due to Getah virus infection. FIGURE 2: Submandibular lymphadenopathy associated with Getah virus infection. Infectious Diseases of the Horse Clinical signs Clinical infection caused by Getah virus has been observed almost exclusively in the horse. Outbreaks of the disease in horses have been sporadic, and have not been associated with any mortality (Fukunaga et al. 2000). The morbidity rate in one outbreak of infection in racehorses was 38% (Kamada et al. 1980; Sentsui and Kono 1980a), with slow and irregular spread of infection. The clinical signs associated with Getah virus infection in horses vary depending on the strain of virus and viral dose (Timoney 2004). Some infections only produce a febrile response with associated inappetence and depression (Sentsui and Kono 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 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 3: Urticaria due to Getah virus infection. EVE Man 08-047 Mair v2:Layout 1 14/08/2009 11:28 Page 157 Getah virus infection have had the disease during gestation are normal (Brown and Timoney 1998). In experimental infections, the clinical signs are similar, but infected horses also commonly develop a serous nasal discharge (Kamada et al. 1991). Diagnosis In view of its clinical similarity to a range of other infectious and noninfectious equine diseases, a provisional clinical diagnosis must be confirmed through laboratory examination. Included in a differential diagnosis of Getah virus infection are equine viral arteritis, equine rhinopneumonitis, equine encephalosis, equine influenza, equine infectious anaemia, African horse sickness fever, purpura haemorrhagica and hoary alyssum toxicosis. Virus isolation or demonstration of viral nucleic acid by reverse-transcription polymerase chain reaction may be performed on nasal swabs, unclotted blood or saliva of acutely infected animals (Kamada et al. 1980; Sentsui et al. 1980; Fukunaga et al. 1981a). The virus can be cultivated in a range of equine and nonequine cell culture systems, especially Vero and RK-13 cell lines, as well as in suckling mice inoculated by the intracerebral route. Highest rates of virus isolation have been achieved from plasma (Fukunaga et al. 1981b). Detection of Getah virus is optimal where specimens are collected as early as possible after the onset of fever. Serum antibodies to Getah virus can be detected by haemagglutination inhibition, complement fixation, enzyme-linked immunosorbent assay (ELISA) and neutralisation tests (Kamada et al. 1980; Sentsui and Kono 1980; Sentsui and Kono 1985; Brown and Timoney 1998). If possible, paired samples taken during the acute and convalescent stages of the disease should be assayed. The neutralisation test is considered the most specific test at differentiating Getah virus infection from other antigenically related alphaviruses (Chanas et al. 1977). Control Control of Getah virus in endemic areas relies on control of the mosquito vector (Fukunaga et al. 2000; Timoney 2004). This can be achieved by eliminating or reducing mosquito breeding sites, and use of larvicides and adulticides. The risk of exposure of 157 horses to virus-infected mosquitoes can be reduced by housing them during dusk and at night. An inactivated whole-virus vaccine is available in Japan. Horses receive an annual booster dose of the vaccine in May or June, prior to the onset of the mosquito season. No epidemics of Getah virus infection have been recorded in horses in Japan since the current vaccination programme was implemented in 1979 (Timoney 2004). References Berge, T.O. (1975) International catalogue of arboviruses, including certain other viruses of vertebrates. In: DHEW Publication No (CDC) 78-8301. US Department of Health, Education and Welfare, Public Health Service, Washington DC. p 278. Brown, C.M. and Timoney, P.J. (1998) Getah virus infection in Indian horses. Trop. Anim. Hlth. Prod. 30, 241-252. Calisher, C.H. and Walton, T.E. (1996) Getah virus infections. In: Virus Infections of Equines, Ed: M.K. Studdert, Elsevier, Amsterdam. pp 157-165. Calisher, C.H., Shope, R.E., Brandt, W., Casals, J., Karabatsos, N., Murphy, F.A., Tesh, R.B. and Wiebe, M.E. (1980) Proposed antigenic classification of registered arboviruses: Togavitidae, alphavirus. Intervirol. 14, 229-232. Chanas, A.C., Johnson, K.B. and Simpson, D.I.H. (1977) A comparative study of related alphaviruses – a naturally occurring model of antigenic variation in the Getah sub-group. J. Gen. Virol. 35, 455-462. Doherty, R.L., Gorman, B.M., Whitebread, R.H. and Carley, J.G. (1966) Studies of arthropod-borne virus infections in Queensland: V. Survey of antibodies to Group A arboviruses in man and other animals. J. expt. Biol. Sci. 44, 365-378. Fukunaga, Y., Kumanomido, T. and Kamada, M. (2000) Getah virus as an equine pathogen. Vet. Clin. N. Am.: Equine Pract. 16, 605-617. Fukunaga, Y., Ando, Y., Kamada, M., Imagawa, H., Wada, R., Kumanomido, T., Akiyama, Y., Watanabe, O., Niwa, K., Takenaga, S., Shibata, M. and Yamamoto, T. (1981a) An outbreak of Getah virus infection in horses – clinical and epizootological aspects at the Miho Training Center in 1978. Bulletin of the Equine Research Institute 18, 94-102. Fukunaga, Y., Kumanomido, T., Imagawa, H., Ando, Y., Kamada, M., Wada, R. and Akiyama, Y. (1981b) Isolation of picornavirus from horses associated with Getah virus infection. Jap. J. vet. Sci. 43, 569-572. Imagawa, H., Ando, Y., Kamada, M., Sugiura, T., Kumanomido, T., 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. Kamada, M., Ando, Y., Fukunaga, Y., Kumanomido, T., Imagawa, H., Wada, R. and Akiyama, Y. (1980) Equine Getah virus infection: Isolation of the virus from racehorses during a enzootic in Japan. Am. J. Trop. Med. Hyg. 29, 984-988. Kamada, M., Kumanomido, T., Wada, R., Fukunaga, Y., Imagawa, H. and Sugiura, T. (1991) Intranasal infection of Getah virus in experimental horses. J. vet. Med. Sci. 53, 855-858. EVE Man 08-047 Mair v2:Layout 1 14/08/2009 11:28 Page 158 158 Sentsui, H. and Kono, Y. (1980a) An epidemic of Getah virus infection among racehorses: Isolation of the virus. Res. vet. Sci. 29, 157-161. Sentsui, H. and Kono, Y. (1980b) Survey of antibody to Getah virus in horses in Japan. Natl. Inst. anim. Health Q. 20, 39-43. Sentsui, H. and Kono, Y. (1985) Reappearance of Getah virus infection among horses in Japan. Jap. J. vet. Sci. 47, 333-335. Infectious Diseases of the Horse race tracks from 1991 to 1997 in Japan. J. vet. Med. Sci. 61, 877-881. Timoney, P.J. (2004) Getah virus infection. In: Infectious Diseases of Livestock, 2nd edn., Eds: J.A.W. Coetzer and R.C. Tustin, Oxford University Press, Cape Town. pp 1023-1026. 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) Serological evidence for the transmission of Getah virus in Hong Kong. Vet. Rec. 134, 527-528. E.B., Estes, M.K., Lemon, S.M., Maniloff, J., Mayo, M.A., Sugiura, T. and Shimada, K. (1999) Seroepizootological survey of Japanese encephalitis virus and Getah virus in regional horse Report of the International Committee on Taxonomy of Viruses, McGeoch, D.J., Pringle, C.R. and Wickner, R.B. (2000) Virus taxonomy: Classification and nomenclature of viruses. In: 7th Academic Press, San Diego. pp 884-887.