Equine influenza

GENERAL INTRODUCTION: ORTHOMYXOVIRIDAE

Introduction

Equine influenza is an acute and highly contagious respiratory disease of horses, donkeys, mules and zebras caused by infection with type A influenza viruses.

Epidemics of acute respiratory disease in horses have been reported for several centuries,^{36, 88} but it was only in 1956 during a widespread epidemic among horses in eastern Europe that the first isolate of equine influenza virus was recovered.⁷³ The virus, characterized as H7N7, was designated as influenza A/equine/Prague/56 and caused epidemics during the 1960s and 1970s.³⁴

In the early spring of 1963 a major epidemic occurred in the USA which was caused by an influenza A virus of a different antigenic subtype, H3N8.^{34, 86} This novel virus, designated as influenza A/equine/Miami/63, was probably introduced into the equine population of Florida with the importation of horses from Argentina.¹⁰² Isolation of an H3N8 virus was also made from South American horses in 1963.⁸⁶ Equine H3N8 was subsequently introduced into France towards the end of 1964,^{10, 11, 35} where it spread rapidly through Europe in the late winter and spring of 1965.³⁴ H3N8 was repeatedly isolated from horses involved in an epidemic that spread throughout the USA and Canada in 1965¹³ and in the same year horses in England experienced influenza, but this was caused by an H7N7 virus.³⁴

There have been numerous reports of outbreaks of equine influenza in Europe, North America and many other countries since the emergence of the H3N8 subtype.^{3, 10, 11, 18, 19, 46, 48, 55, 66, 67, 69, 70, 82, 95, 99, 104} However, equine H7N7 viruses have not been isolated since 1980 and are considered extinct.⁹⁷ In contrast, H3N8 viruses continue to cause severe respiratory disease among non-vaccinated horses. Periodically, as occurred in Europe in 1979 and 1989 and Japan in 2007, there are large epidemics even among recently vaccinated horses associated with significant antigenic changes in H3N8 viruses.^{48, 67, 104} Following the outbreak in Europe in 1989 in which there was significant failure of vaccines to prevent infection, there was a further divergence of H3N8 viruses into two antigenically distinct lineages (so-called American and Eurasian, due to their initial geographic distributions). Field and experimental studies provided increasing evidence of failure of inactivated viruses of these two lineages to cross-protect. At the time this confirmed the importance of including representative viruses of both lineages in vaccines. These studies also showed the importance of updating vaccines by replacing older outdated vaccine strains with more recent and epidemiologically relevant viral strains. This led to the establishment of an Expert Surveillance Panel (ESP) for vaccine strain selection.²³ The ESP includes representatives from OIE reference laboratories and WHO experts. The panel review surveillance data collected by both OIE reference- and collaborating laboratories from around the world on an annual basis. The panel makes recommendations on which strains should be included in vaccines, which are published by the OIE.

Eurasian lineage strains (subtypes) have not been isolated since 2005 and are no longer thought to circulate. Consequently, there is no longer a requirement to include a Eurasian lineage strain in vaccines.⁷² Meanwhile, the American lineage evolved further into three sub-lineages: Kentucky, Florida and South American.⁵³ In the early 2000s the Florida sub-lineage diverged into clades 1 and 2, which are antigenically and genetically distinct.¹⁵ Although clade 1 viruses have predominantly been isolated from North America, they have been responsible for causing large outbreaks in South Africa, Japan, Australia and South America and in recent years there have been isolated from outbreaks in Europe.^{3, 5, 14, 16, 38, 40, 48, 80, 104} In contrast, the majority of clade 2 viruses have been isolated from horses in Europe and Asia.^{15, 32, 37, 84, 95, 101, 107} Reassortment between the different lineages, sub-lineages and clades of H3N8 has also been reported.^{15, 64, 65, 101} For example, viruses encoding a clade 1 haemagglutinin (HA) and clade 2 neuraminidase (NA) have previously been isolated in the UK, revealing evidence of co-infection with the two clades.¹⁰¹ The current OIE-recommendation is to include an example of each clade in vaccines.⁷²

Aetiology

Influenza viruses are pleomorphic, spherical or filamentous virions with a diameter of 80 to 120 nm and have a segmented, single-stranded RNA genome of negative sense. The eight gene segments code for two surface glycoproteins; the haemagglutinin (HA, restricted to H when assigning subtypes e.g. H3) and neuraminidase (NA, restricted to N when assigning subtypes e.g. N8), the internal matrix protein and nucleoprotein and other structural and non-structural proteins...