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INFLUENZA
Novel H1N1 influenza in people: global spread from an animal source?
  1. R. M. Irvine, BVetMed, MSc, MRCVS1 and
  2. I. H. Brown, CBiol, MIBiol, PhD1
  1. 1 Virology Department, Veterinary Laboratories Agency – Weybridge, New Haw, Addlestone, Surrey KT15 3NB
  1. Correspondence to Dr Brown

Abstract

Richard Irvine and Ian Brown of the Veterinary Laboratories Agency discuss some epidemiological features of the novel H1N1 influenza virus that is currently causing concern among health authorities worldwide.

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Influenza virus – an ever-changing foe

THE rapidly unfolding and evolving events, on a worldwide scale, relating to the humanto- human transmission of a novel H1N1 influenza A virus have dominated the news media in the past two weeks. In Europe to date, as in North America and Canada, there have been cases of laboratoryconfirmed H1N1 infection in people returning from recent foreign travel in South America, specifically Mexico. In the vast majority of cases in people who are not from Mexico, the reported clinical presentation has been mild. Nevertheless, the emergence of this novel H1N1 influenza virus, and its rapid and worldwide spread, facilitated by the normal movement of people across international boundaries, highlights some important epidemiological features.

It is relevant to note that while this H1N1 influenza virus has been termed ‘swine influenza’ (or ‘swine flu’), the definitive scientific evidence base to support its origin in pig populations has not yet been confirmed. Furthermore, in the absence of contemporaneous reports of clinical disease in pigs infected with this virus, it is not possible to confirm the clinical signs that may be observed in infected animals. In common with other influenza A infections of pigs, where a range of clinical presentations can occur, asymptomatic infection with this virus is also a theoretical possibility.

Influenza A virus ecology with relevance to swine

Influenza A viruses infect a large variety of animal species, including mammals and birds, and, given the worldwide animal-human interface, there is potential for interspecies transmission of influenza viruses in nature. Phylogenetic studies of influenza A viruses have revealed species-specific lineages of viral genes and have also demonstrated that the frequency of interspecies transmission depends on the animal species. Aquatic birds are known to be the source of all influenza viruses for other species. Pigs are an important host in influenza virus ecology as they are susceptible to infection with both avian- and human-origin influenza A viruses, and are often involved in interspecies transmission, facilitated by regular close contact with people and/or birds. Following transmission to and independent spread of avian or human influenza A viruses in pigs, these viruses are generally referred to as being ‘avian-like’ or ‘human-like’ swine influenza viruses, reflecting both their previous and current hosts. After 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 lineages is an invaluable characteristic in studying and determining influenza virus epidemiology.

Epidemiology

The epidemiology of swine influenza in pigs is itself not straightforward. However, a number of consistent features exist:

  • Swine influenza is an important, contagious disease of pigs that occurs worldwide, and is typically caused by infection with influenza A viruses;

  • Virus subtypes H1N1, H1N2 and H3N2 are endemic in many pig populations around the world, and pigs serve as major reservoirs of these viruses;

  • Interspecies transmission, including zoonotic infections, with the recognised endemic swine influenza viruses does occasionally occur (reviewed by Brown 2000).

The maintenance of these influenza viruses in pigs, and the frequent introduction of new influenza viruses from other species, could, therefore, contribute to the generation of strains of human influenza virus with pandemic potential (Alexander and Brown 2000). Historical evidence of this suggests that, to date, the risk has been low

In addition, there is significant genetic and antigenic variability within each of the endemic swine influenza subtypes, which can often be dependent on geographical region. More specifically, before the emergence of this novel H1N1 virus, there has been a clear genetic distinction between North American and Eurasian lineages of swine influenza viruses. This new variant of H1N1 virus contains two of eight gene segments (encoding for the neuraminidase and matrix protein genes) that do not appear typical of the genes seen in current North American strains. It has been postulated that these two gene segments have derived from Eurasian swine influenza viruses.

It is not known if the particular genotype of H1N1 virus that appears putatively to have originated in Mexico is circulating in North American pigs, but its close similarity to other strains of swine influenza known to be circulating in the region (sharing six of eight gene segments) has led to the assumption that this novel H1N1 strain is derived from pigs

Swine influenza: clinical signs and transmission

Infection of pigs with influenza A viruses can cause a spectrum of clinical presentations in pigs, from acute onset, severe respiratory illness that infects a large number of exposed pigs, often with little mortality, to less severe illness that may be characterised as a chronic respiratory disease syndrome, usually affecting groups of pigs. Breeding pigs can also suffer reproductive problems, and pigs can also be infected and not show signs of illness. Recovery in uncomplicated infections is usually quick (within 10 to 14 days). Infection is usually transmitted between pigs over short distances by aerosols generated by infected pigs coughing or sneezing, by direct or indirect contact or by the movement and introduction of asymptomatic infected pigs. Other factors, such as the presence of other infections, can also make disease appear more severe or seem to last longer.

Influenza viruses in pigs in Europe

A number of countries in Europe conduct routine surveillance of pig populations for swine influenza, but, as this is not a notifiable disease in the EU, the surveillance programme is not consistent across the region. A European Swine Network for Influenza in Pigs (ESNIP2), funded by the EU, has been proactively monitoring the influenza situation in the European pig population for several years, and has demonstrated that subtypes H1N1, H3N2 and H1N2 co-circulate.

There are also some significant differences in epidemiology in terms of the virus subtypes involved within the EU. For example, currently in Great Britain (GB) ‘avian-like’ swine H1N1 viruses co-circulate with H1N2, but H3N2 has apparently disappeared since the mid-1990s (see Table 1). This is in contrast, for example, to the situation in Italy, where these viruses are still widespread (Van Reeth and others 2008).

The genotypic diversity of the influenza viruses in the European pig population is also well recognised, and periodically genotypic variants are identified. However, broadly, the endemic strains retain common genotypes and the new reassorted variants appear to have poor viability for long-term sustainability and transmission within the swine population (Brown 2008). This is in contrast to the current situation in North America, where multiple genotypes of several different subtypes have emerged within the past 10 years, creating a complex aetiology with respect to swine influenza in these populations.

Based on current evidence from surveillance programmes in several European countries, the variant of H1N1 virus recently isolated in human beings has never been reported, and therefore does not appear to be present in the European pig population.

Swine influenza surveillance in Great Britain

In Great Britain, the Veterinary Laboratories Agency (VLA) has run a national swine influenza scanning surveillance programme since 1991, funded by Defra. This programme is targeted, based on clear criteria using a standardised case definition, selection algorithm and sampling protocol, and provides free-of-charge laboratory testing for the detection of swine influenza viruses in clinical samples from affected pigs submitted by veterinary surgeons to VLA regional laboratories (RLs) and Scottish Agricultural College (SAC) Veterinary Services. Further information can be found on the VLA website at www.defra.gov.uk/vla/diseases/dis_si.htm, or from local VLA – RLs or SAC disease surveillance centres.

It is important for vigilance to be maintained within both the swine and human sectors for the emergence or spread of the newly reported H1N1 virus. The recent report of human-to-pig transmission in Alberta, Canada, highlights the importance of reverse zoonosis, a recognised phenomenon in influenza virus epidemiology. Ongoing close liaison and collaboration is also occurring between the VLA and public health institutes and delivery agencies to ensure rapid and robust information exchange.

Capacity for change

The global human-animal interface is complex and dynamic, with the potential for zoonotic transmission of known pathogens, variants thereof and new, emergent infectious agents. In turn, animal reservoirs and people, both with the capacity for rapid global movement and distribution in time and space (intrinsic properties of globalisation), face these shared infectious challenges, not forgetting the propensity of some pathogens for two-way exchange between species.

While the novel H1N1 influenza virus is assumed to be of animal origin, it is now clearly spreading between humans and has already entered the EU, as well as other parts of the world. However, to date, human-to-animal transmission of H1N1 infection has not been identified or reported by EU member states. The case of human-to-pig transmission in Canada followed contact of an infected occupationally exposed worker, apparently incubating H1N1 virus infection following return from travel to Mexico. It also seems inevitable that more human cases will be detected worldwide. It is important to note that the potential host range for this virus is currently unknown. Potential changes in the virus characteristics need to be closely monitored by both public health and veterinary institutes.

The world is watching on as international scientific and sociopolitical efforts attempt to better understand and combat an historical foe with seemingly limitless capacity for change and variation, and to evade predictions – the influenza virus.

References

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