VLA Weybridge, Addlestone, Surrey, United Kingdom

A disease capable of causing extremely high mortality amongst infected fowls was first defined in 1878 and became known as 'fowl plague'. The causative organism of this disease was shown to be a ‘virus’ as early as 1901 but it was not until 1955 that the relationship of this and other milder viruses isolated from birds with mammalian influenza A viruses (first isolated in the 1930s) was demonstrated (1). Only type A influenza viruses are known to cause natural infections of birds, but viruses of all 15 HA and all 9 NA influenza A subtypes in the majority of possible combinations have been isolated from avian species.

Influenza A viruses infecting poultry can be divided into two distinct groups on the basis of their ability to cause disease. The very virulent viruses cause ‘fowl plague’, now termed highly pathogenic avian influenza [HPAI], in which mortality may be as high as 100%. These viruses have been restricted to subtypes H5 and H7, although not all viruses of these subtypes cause HPAI. All other viruses cause a much milder, primarily respiratory, disease, which may be exacerbated by other infections or environmental conditions.

The haemagglutinin glycoprotein for influenza viruses is produced as a precursor, HA0, which requires post translational cleavage by host proteases before it is functional and virus particles are infectious (2). The HA0 precursor proteins of avian influenza viruses of low virulence for poultry have a single arginine at the cleavage site and are limited to cleavage by host proteases such as trypsin-like enzymes and thus restricted to replication at sites in the host where such enzymes are found, i.e. the respiratory and intestinal tracts. HPAI viruses possess multiple basic amino acids [arginine and lysine] at their HA0 cleavage sites and appear to be cleavable by a ubiquitous protease[s] probably one or more proprotein-processing subtilisin-related endoproteases of which furin is the leading candidate (3). These viruses are able to replicate throughout the bird, damaging vital organs and tissues which results in disease and death.

The first isolation of influenza virus from feral birds was in 1961 from common terns (Sterna hirundo) in South Africa (4), but it was not until the mid-1970s that any systematic investigation of influenza in feral birds was undertaken. These revealed the enormous pools of influenza viruses now known to be present in the wild bird population.

Virus isolations from other wild birds have been completely overshadowed by the number, variety and widespread distribution of influenza viruses in waterfowl, Order Anseriformes. In the surveys listed by Stallknecht and Shane (5) a total of 21,318 samples from all species resulted in the isolation of 2,317 (10.9%) viruses. Of these samples 14,303 were from birds of the Order Anseriformes and yielded 2,173 (15.2%) isolates. The next highest isolation rates were 2.9% and 2.2% from the Passeriformes and Charadriiformes and the overall isolation rate from all birds other than ducks and geese was 2.1%.

Since 1975 when the first isolates from caged birds were recorded, isolates, from all sources, have been mainly of H4 or H3 subtypes. The majority of influenza viruses from caged birds come from passerine species and only rarely are psittacines infected. Although the presence of influenza viruses in birds held in quarantine is monitored continually in several countries around the world, there appear to have been periods, often lasting several years when no isolations have been made.

Domestic poultry.

Since 1959 primary outbreaks of HPAI in poultry have been reported 17 times, five in turkeys and 12 in turkeys; 8 of these outbreaks have occurred since 1990 (Table 1).

During 1994-99 infections of poultry with influenza viruses of H9N2 subtype appear to have been common world-wide. Outbreaks occurred in Germany in 1995-96, Italy in 1994, Ireland in 1997, South Africa in 1995, and Korea in 1996 (6). Since 1997 serious problems associated with H9N2 virus have been reported in Iran, Saudi Arabia, Pakistan, China and other Asian countries.

Chickens.

At the end of the 19th and early 20th Centuries ‘fowl plague’ was often reported in chickens and in several countries this disease was probably enzootic. However, in the second half of the 20^th Century reports of influenza infections of chickens have been rare compared to infections of other domestic poultry despite the much higher populations of chickens. For example in the USA, despite frequent influenza epizootics in turkeys in some states, between 1964 and 1982 only three outbreaks in chickens were recorded (7).

Despite the low incidence of influenza infections of chickens throughout the world there have been 12 outbreaks of HPAI since 1959 and significant spread occurred in Pennsylvania and neighbouring states in the USA during 1983-1984 and in Mexico and Pakistan in 1994/95. Other outbreaks since 1959 have shown no or extremely limited spread. Eight HPAI outbreaks in backyard poultry flocks infected with H5N2 virus were reported in Italy in 1997/8. Outbreaks of H5N1 HPAI occurred on three farms in Hong Kong during March-May 1997 with 70-100% mortalities (8) and subsequent spread to live bird markets.

Since 1963, most of the major turkey-producing countries have had disease problems associated with influenza infections. In the USA in California and Minnesota, where turkey farms are heavily concentrated and situated on migratory waterfowl flyways, influenza virus infections have been seen regularly, but in other countries outbreaks in turkeys have been usually restricted to one or two isolated incidents in the years recorded. Despite the greater prevalence of influenza viruses in turkeys, of the 17 reported isolations of HPAI since 1959 only five were apparently primarily from turkeys (Table 1).

Commercial ducks.

The influenza status of commercial ducks in most countries is poorly understood or has not been investigated. When surveillance of commercial ducks has been undertaken, enormous pools of virus and many subtype combinations have been detected.

The increase in trade in ostriches and other ratites during the 1990s led to the movement of large numbers of such birds around the world and the testing for viruses, including influenza, has resulted in the regular isolation of influenza viruses from these birds. Since the first reported isolations of influenza viruses from ratites in 1991 viruses of H3N2, H4N2, H4N6, H5N2, H5N9, H7N1, H7N3, H9N2, H10N4 and H10N7 subtypes have been isolated. All these were of low virulence for chickens.

Other domestic poultry.

Other commercially reared birds represent a very small proportion of domestic poultry in most countries. Some such birds (e.g. pheasants and geese) are reared under semi-wild conditions. Isolations of influenza viruses have been reported from muscovy ducks (Cairinia moschata), mallard ducks (Anas platyrhyncos), pheasants (Phasianus spp.), Japanese quail (Coturnix coturnix japonica), chukars (Alectoris chukar), guinea fowl (Numida meleagris), and various types of goose.

1. Schafer, W. (1955). Vergleichende sero-immunologischs Untersuchungen uber die viren der influenza und klassichen Geflugelpest. Zeitschrift fur Naturfoirschung, 10b, 81-91.
2. Rott, R. (1992): The pathogenic determinant of influenza virus. Veterinary Microbiology 33, 303-310.
3. Stieneke-Grober, A., M. Vey, H. Angliker, E. Shaw, G. Thomas, C. Roberts, H-D. Klenk, and W. Garten. (1992). Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin endoprotease. EMBO Journal 11, 2407-2414.
4. Becker, W.B. (1966). The isolation and classification of tern virus: Influenza virus A/tern/South Africa/1961. J. Hyg., 64, 309-320.
5. Stallknecht, D.E. and Shane, S.M. (1988). Host range of avian influenza virus in free-living birds. Vet. Res. Commun. 12, 125-141.
6. Alexander, D.J. and Gough, R.E. (1997) Virus diseases of the respiratory organs: World situation and recent developments. Proceedings of the XI International Congress of the World Veterinary Poultry Association. Acta Vet. Hung. 45, supplement 1-22.
7. Pomeroy, B.S. (1982). Avian influenza in the United States (1964-1980). Proceedings of the First International Symposium on Avian Influenza, 1981. Carter Composition Corporation, Richmond, USA, pp. 13-17
8. Claas, C.J., Osterhaus, A.D.M., Beek, R., De Jong, J., Rimmelzwaan, G.F., Senne, D.A., Krauss, S., Shortridge, K.F. and Webster, R.G. (1998). Human influenza A H5 N1 virus related to a highly pathogenic avian influenza virus. Lancet 351 472-477.