Influenza generally appears with the introduction of infected pigs into a herd, either through the movement or mixing of infected pigs with susceptible animals. Transmission from pigs to humans and humans to pigs occurs occasionally, but only rarely from avian species. Once a herd is infected with a virus which is able replicate, irrespective of its origin, the virus persists through the production of young susceptible pigs and the introduction of new stock, often leading to the herd becoming infected endemically. Following the introduction of an influenza virus, well adapted and pathogenic to pigs, into a fully susceptible herd, there may be clinical symptoms in affected pigs and rapid spread

Part 1: swine, avian & human influenza viruses
by
Dr. Ian H. Brown
OIE/FAO/EU International Reference Laboratory for Avian Influenza
Veterinary Laboratories Agency, Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK

Reservoirs of influenza A viruses

Influenza A viruses infect a large variety of animal species (Alexander 1982; Webster et al 1992) including humans, pigs, horses, sea mammals and birds. Given the worldwide interaction between humans, pigs, birds and other mammalian species there is a high potential for cross-species transmission of influenza viruses in nature. Phylogenetic studies of influenza A viruses have revealed species-specific lineages of viral genes and have demonstrated that the prevalence of interspecies transmission depends on the animal species (Webster et al 1992). Aquatic birds are known to be the source of all influenza viruses for other species.

Pigs are an important host in influenza virus ecology since they are susceptible to infection with both avian and human influenza A viruses, often being involved in interspecies transmission, facilitated by regular close contact with humans or birds. Following the transmission to, and independent spread of avian or human influenza A viruses in pigs, these viruses are generally referred to as ‘avian-like’ swine or ‘human-like’ swine, reflecting their previous host, and following genetic reassortment with other influenza A viruses, some of the genes of these viruses may be maintained in the resulting progeny viruses. Therefore, the evolution of influenza genes in species-specific gene lineages is an invaluable characteristic in studying influenza virus epidemiology.

 

Early history of Swine Influenza

Swine influenza (SI) was first observed in 1918 in the United States, Hungary and China (Beveridge 1977; Chun 1919; Koen 1919). It coincided with an influenza pandemic in humans, which was the most severe of modern times, accounting for at least 20 million deaths worldwide.

Those who first noticed the disease in pigs, recognised similarities between the porcine and human disease and suggested they had a common aetiology. Later retrospective serological investigations confirmed that the disease in humans and pigs had been caused by closely related influenza A viruses in both cases. The causative agent was an H1N1 influenza A virus which had possibly derived from a common ancestor (Gorman et al 1991; Kanegae et al 1994; Reid et al 1999). Genetic sequencing studies of the haemagglutinin (HA) gene of the human virus revealed that the virus most probably spread from humans to pigs and is supported by observations from veterinarians who did not describe the disease in pigs until just after its appearance in humans. Although the disease in pigs was described during the following years (Dorset et al 1922; McBryde 1927), it was not until 1930 that the virus was isolated and identified (Shope 1931).

 

Epidemiology

Influenza A viruses of subtypes H1N1 and H3N2 have been reported widely in pigs, associated frequently with clinical disease. These include classical swine H1N1, ‘avian-like’ H1N1 and ‘human’- and ‘avian-like’ H3N2 viruses (see table 1). These viruses have remained largely endemic in pig populations worldwide and have been responsible for one of the most prevalent respiratory diseases in pigs. Although usually regarded as an endemic disease, epidemics may result when influenza infection occurs in an immunologically naive population (which can be linked to significant antigenic drift) or through exacerbation by a variety of factors such as poor husbandry, secondary bacterial or viral infections and cold weather.

Serosurveillance results in Great Britain indicated that more than half of adult pigs in the national population had been infected with one or more influenza A viruses during their lifetime, including fourteen per cent of pigs which had been infected with influenza viruses of both human and swine origin (Brown et al 1995b).

Table 1. Phenotypes of influenza A viruses infecting pigs endemically worldwide.

Subtype	Location	Comments
H1N1	North America	‘Classical’ virus, first isolated in 1930 in North America
	Europe
	Asia
	South America
	Europe	‘Avian-like’ virus, first isolated in 1979
	Asia	‘Avian-like’ virus, first isolated in 1993
H3N2	Asia	‘Human-like’ virus, first isolated in 1970
	Europe	in Asia.
	North America
	South America
	Africa
	Asia	‘Avian-like’ virus, first isolated in 1978
H1N2	Asia	Classical/‘human-like’ reassortant in Japan
	Europe	Human/‘human-like’ reassortant in GB

Classical H1N1

Following the reported occurrence of influenza in pigs at the time of the 1918 pandemic, SI was for a long time apparently confined to the north and mid west of the United States, where, after its first appearance, annual outbreaks occurred during the winter months. These and viruses related closely are termed classical viruses. Elsewhere SI was observed much later with the situation being frequently complicated by the association of other agents with respiratory disease. However, classical swine influenza viruses, or their antibodies, have been reported from many parts of the world including Canada (Morin et al 1981) Brazil (Cunha et al 1978), Hong Kong (Yip 1976), Japan (Yamane et al 1978), India (Das et al 1981), China, Taiwan (Shortridge and Webster 1979), Kenya (Scott 1957) and Iran (Samadieh and Shakeri 1976).

In Europe, virus isolations were made in the United Kingdom (Blakemore and Gledhill 1941a, b) and Czechoslovakia (Harnach et al 1950), whilst at this time antibodies to H1N1 influenza viruses were demonstrated in pigs in the Federal Republic of Germany (Kaplan and Payne 1959).

After these episodes the virus apparently disappeared from these countries and there was no evidence of infections in Europe for nearly twenty years, until 1976 when classical swine influenza virus was isolated from disease outbreaks in northern Italy.

The viruses isolated were related closely to classical swine influenza virus from the United States (Nardelli et al 1978), and it is probable that the virus was introduced via imported pigs from the United States. The infection was limited to northern Italy until 1979, when SI caused by classical swine influenza virus was reported from Belgium (Biront et al 1980; Vandeputte et al 1980) and France (Gourreau et al 1980).

The disease spread rapidly to other European countries and has been reported from the Netherlands (Masurel et al 1983), Germany (Ottis et al 1981; Witte et al 1981), Denmark (Sorensen et al 1981), Sweden (Martinsson et al 1983; Abusugra et al 1987) and the United Kingdom (Roberts et al 1987). This virus became endemic in pigs throughout Europe with a seroprevalence of 20 to 25 per cent (Zhang et al 1989; Brown et al 1995b) but following the emergence of ‘avian-like’ H1N1 virus its continued circulation throughout Europe is uncertain.

Easterday (1980a) considered that the natural history of SI has remained largely stable for a period of at least sixty years, the virus being maintained relatively unchanged both antigenically and genetically through this period of time. Serological studies of pigs in the United States have shown that classical swine H1N1 influenza virus was prevalent throughout the pig population, with approximately 25 per cent of fattening pigs having evidence of infection (Hinshaw et al 1978) whilst amongst the longer lived breeding population this figure rises to 45% (Easterday 1980b).

Marked regional variation in prevalence has been demonstrated and in north-central United States an average prevalence of 51 per cent has been reported (Chambers et al 1991). In Asia, classical H1N1 viruses are apparently the predominant influenza virus infecting pigs (Guan et al 1996).

‘Human-like’ viruses

Infections of pigs with the prevailing human subtypes also occur under natural conditions. Shope (1938) presented serological evidence that human to pig transmission could occur, but it was not until the isolation of Hong Kong H3N2 virus from pigs in Taiwan in 1970 (Kundin 1970) that investigations began to examine the potential transmission of human strains to pigs. Although no disease was reported among infected pigs, in the next several years H3N2 viruses were isolated regularly from pigs (Tumova et al 1976; Shortridge and Webster 1979; Nerome et al 1981; Ottis et al 1982) and/or antibody was demonstrated (Harkness et al 1972; Tumova et al 1976; Arikawa et al 1979) in swine populations throughout the world.

H3N2 influenza A viruses related to a human strain from 1973, continued to circulate in European pig populations long after their disappearance from the human population. Since 1984, outbreaks of clinical influenza in pigs due to a H3N2 influenza A virus, related antigenically to human strains from the early to mid 1970’s, have been observed throughout Europe (Aymard et al 1985; Haesebrouck et al 1985; Pritchard et al 1987) with infections frequently characterised by high seroprevalence (Lange et al 1984; Tumova et al 1980; Robert et al 1987). This apparently high level of H3N2 infections in Europe is in sharp contrast to the low prevalence in pigs in North America which suggests that the virus is not established in the American swine populations, but occurs only by infrequent introduction from infected humans (Easterday 1980a). Until recently virus has been isolated rarely from pigs in the United States (Chambers et al 1991) and only since 1990 from pigs in Canada (Bikour et al 1994) which might reflect different epizootiological patterns in different areas worldwide.

Human H1N1 viruses can also infect pigs, but although pig to pig transmission has been demonstrated under experimental conditions (Kundin and Easterday 1972), most strains are not readily transmitted among pigs in the field (Hinshaw et al 1978).

Serological surveillance studies worldwide suggest that the prevailing human H1N1 strains are readily transmitted to pigs (Roberts et al 1987; Brown et al 1995b) and have resulted occasionally in the isolation of virus (Katsuda et al 1995a), but are not apparently maintained in pigs independently of the human population.

‘Avian-like’ viruses

Since 1979 the dominant H1N1 viruses in European pigs have been ‘avian-like’ H1N1 viruses which are antigenically and genetically distinguishable from North American classical swine H1N1 influenza viruses, but related closely to H1N1 viruses isolated from ducks (Pensaert et al 1981; Scholtissek et al 1983). All of the gene segments of the prototype viruses were of avian origin (Schultz et al 1991) indicating that transmission of a whole avian virus into pigs had occurred, and as a result have been implicated as the possible precursors of the next human pandemic virus (Ludwig et al 1995). These ‘avian-like’ viruses appear to have a selective advantage over classical swine H1N1 viruses which are related antigenically, since in Europe they have replaced classical swine influenza virus (Bachmann 1989; Campitelli et al 1997). Within two years of the introduction of ‘avian-like’ viruses into pigs in Great Britain, classical swine H1N1 apparently disappeared as a clinical entity. More recently an independent introduction of H1N1 virus from birds to pigs has occurred in southern China and these viruses have been detected in pigs in south east Asia since 1993 (Guan et al 1996) where they are currently cocirculating with classical H1N1 viruses.

Phylogenetic analysis of the genes of these viruses has revealed that they form an Asian sublineage of the Eurasian avian lineage. In addition, some of the H3N2 viruses isolated from pigs in Asia since the 1970’s have been entirely ‘avian-like’ (Kida et al 1988) and have been introduced apparently from ducks, although their association with epizootics of respiratory disease in pigs is unproven.

H1N2 viruses

Influenza A H1N2 viruses, derived from classical swine H1N1 and ‘human-like’ swine H3N2 viruses have been isolated in Japan (Sugimura et al 1980) and France (Gourreau et al 1994). In Japan, these viruses appear to have spread widely within pigs and are associated frequently with respiratory epizootics* (Ouchi et al 1996). Subsequently an H1N2 influenza virus (see Genetic reassortment) related antigenically to human and ‘human-like’ swine viruses has emerged and become endemic in pigs in GB (Brown et al 1995a) often in association with respiratory disease. [* epizootic = an epidemic in animals]

Outbreak course and persistence in pigs

Swine husbandry practises influence directly the evolution of influenza viruses in pigs leading generally to reduced genetic drift, particularly in the genes encoding HA and neuraminidase (NA), compared to those of similar viruses in the human population. SI generally appears with the introduction of new pigs into a herd, thereby being related to the movement of animals from infected to susceptible herds.

Once a herd is infected the virus is likely to persist through the production of young susceptible pigs and the introduction of new stock (Fig.1). Complete depopulation is the only effective measure for eliminating the disease. Once a herd becomes infected with SI it is likely to be maintained with annual episodes of acute disease.

There may be differences in the epizootiology of SI between the United States and Europe. In Europe many herds may harbour virus without showing clinical signs (Bachmann 1989).

The disease often appears simultaneously on several farms within an area. Such multicentric outbreaks are not necessarily the result of recent movement of infected animals, but due to the widespread distribution of the virus among herds in an area.

The primary route of virus transmission is through pig to pig contact via the nasopharyngeal route, the virus being shed in nasal secretions and disseminated through droplets or aerosols.

Close contact between pigs (often enhanced through husbandry practises), stressful situations, meteorological and environmental factors are conducive to the spread of influenza viruses.

Outbreaks of disease occur throughout the year but usually peak in the colder months (Easterday 1980a). Infection with swine influenza H1N1 virus is frequently subclinical, and typical signs are seen often in only 25 to 30 per cent of a herd. Blaskovic et al (1970) showed that swine influenza H1N1 virus was excreted from one infected pig for over four months, although 7 to 10 days is typical.

Continuous circulation of influenza viruses within a herd without the apparent need for an intermediate host has been shown by the isolation of virus from a herd the year round (Nakamura et al 1972). Furthermore, swine influenza H1N1 virus has been recovered from pigs with no signs of disease (Hinshaw et al 1978).

The interepizootic survival and the potential existence of reservoirs for the virus have been studied extensively. There are no clear data to support or reject the existence of a long-term true carrier state of influenza viruses in pigs, but the widespread occurrence of the virus in pigs themselves and the methods of swine husbandry make it likely that the virus is maintained by continual passage to young susceptible pigs.

 

Swine Flu Part 2: Transmission between pigs and other species: Review

Highly Pathogenic Avian Influenza Virus Spreads Birds, People, Pigs: Bird 'Flu