Getah virus infection

Previous authors: P J TIMONEY

Current authors:
H BANNAI - Fellow, PhD, DVM, 1400-4 Shiba, Shimotsuke, Tochigi, 329-0412, Japan
T KONDO - Chief of Research Planning & Coordination Division, DVM, PhD, Equine Research Institute, Japan Racing Association, 1400-4, Shiba, Shimotsuke, Tochigi, 329-0412, Japan
P J TIMONEY - Professor, MVB (Hons), MS, PhD, FRCVS, Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, 40546 - 0099, USA

Introduction

Getah virus is an arbovirus that was first isolated from Culex gelidus mosquitoes collected near Kuala Lumpur, Malaysia, in 1955.⁴ The name of the virus is thought to be derived from the Malaysian word for rubber, ‘getah’. This relates to the fact that mosquitoes from which the original isolation of Getah virus was made were collected under a mature rubber tree canopy on a rubber plantation.²² For many years following its initial isolation there was no evidence that the virus was pathogenic for humans or animals. It was not until 1978, following an epidemic of a mild, self-limiting illness among racehorses in Japan that Getah virus was shown to be capable of causing disease.^{18, 33} Since then, the virus has been shown to be pathogenic for other species of livestock. It has been infrequently identified with foetal infection in pregnant sows as well as illness and death in new-born piglets.^{37, 43}

Additional outbreaks of Getah virus infection in horses occurred at racetracks and training facilities in Japan in 1979 and 1983.³⁶ For more than three decades, no outbreaks of the infection were recorded among Japanese horses. However the disease reoccurred in 2014 with an outbreak among racehorses at a training facility in Japan.³⁰ This was followed by outbreaks at the same facility in 2015 and 2016.^{3, 29} With the exception of an extensive outbreak on a Thoroughbred breeding farm in India in 1990,⁵ there have been no reported occurrences of Getah virus infection outside Japan.  To date, there is no evidence to indicate that Getah virus is a human pathogen.¹¹

Aetiology

Getah virus is an enveloped, positive-stranded RNA virus belonging to the genus Alphavirus of the family Togaviridae.⁷ Based on amino acid sequence analysis of the E1 viral structural protein,³⁹ it has been classified in the Semliki Forest complex together with Semliki Forest, Bebaru, Ross River, Chikungunya, O’nyong-nyong, Una and Mayaro viruses.⁴¹

Getah virus is a relatively small virus, with a particle diameter of 66 to 70 nm¹⁸ and comprising two envelope proteins, E1 and E2, together with a core protein.³⁴ Like many other RNA viruses that replicate as quasi-species, Getah virus can undergo frequent mutations in nature and when passaged both in vivo and in vitro.^{8, 28, 38} The virus possesses haemagglutinating and complement-fixing antigens which have been used to develop diagnostic tests for this infection and, together with the neutralization test, to investigate antigenic relationships between different strains and subtypes of the virus.¹¹

Apart from horses and pigs, serological evidence of Getah virus infection has been found in a large number of vertebrate species (mammals, birds and reptiles) in nature.^{12, 26, 27} Experimentally, the virus has been transmitted to mice, hamsters, guinea pigs and rabbits.^{1, 24} Transplacental infection can occur in pregnant mice and hamsters.^{1, 35}

In vitro, Getah virus can replicate in a range of equine and non-equine cell culture systems, e.g. Vero, BHK-21, RK- 13, MA-104, MDBK, LLC-MK2 and MDCK,¹⁹ including certain mosquito cell lines, e.g. C6/36.¹⁴

The infectivity of Getah virus is readily destroyed by exposure to lipid solvents¹⁹ and to dry, hot, acidic or alkaline conditions (pH <5 or >10).³¹ However, the virus can remain viable for years in a lyophilized state.⁶

Epidemiology

Getah virus is mosquito-borne and is widely distributed throughout Southeast Asia and surrounding areas, including Australia, Borneo, Cambodia, China, India, Indonesia, Japan, Korea, Malaysia, Mongolia, the Philippines, Russia, Thailand, Sarawak, Siberia, Sri Lanka and Vietnam.^{6, 11} While most Getah virus isolations from mosquitoes have been from Culex spp., the virus has also been frequently isolated from Aedes spp., especially in Japan.¹¹

With the exception of infrequently encountered outbreaks or cases of clinical disease in horses and pigs,^{5, 18, 34, 36, 37, 43} natural infection in other domestic or wildlife species is believed to be subclinical.¹¹

In tropical areas of Asia, Getah virus is thought to be maintained year-round in a mosquito–pig–mosquito cycle.⁶ Based on levels and duration of viraemia, pigs appear to play an important role as amplifying hosts in endemic regions.¹¹ The role of other vertebrates such as rodents or birds as amplification or reservoir hosts of Getah virus is currently undetermined. Whether there is transtadial or transovarial transmission of the virus in mosquitoes is also not known.⁶

Various serological surveys on the distribution and prevalence of Getah virus infection in horses in Japan have shown that the virus is widespread in the country, with seropositivity rates of neutralizing antibodies ranging from 3 to 72 per cent.^{16, 34} It appears that many cases of Getah virus infection in horses are subclinical.¹¹

Transmission of Getah virus is primarily by mosquitoes.^{4, 31} Depending on the region of...