On October 17, 2013, EFSA published scientific opinion on the possible risks posed by the influenza A (H3N2v) virus for animal health and its potential spread and implications for animal and human health.
Following a request from the European Commission, the Panel on Animal Health and Welfare (AHAW) was asked to deliver a scientific opinion on the possible risks posed by the Influenza A(H3N2)v virus for animal health and its potential spread and implications for animal and human health.
In 2011, the United States of America reported a cluster of cases of human infection with a swineorigin influenza A(H3N2) variant virus H3N2v containing the matrix (M) gene from the 2009 H1N1 pandemic virus (A(H1N1)pdm09). In 2012, 309 influenza H3N2v virus infections in humans were identified in the US and 12 cases in 2013. Most of the human infections occurred in persons that had contact with live pigs at county fairs, especially children.
Swine are an important host in influenza virus ecology since they are susceptible to infections with both avian and human influenza A viruses and can play a role in interspecies transmission. This can lead to co-infection and genetic reassortment of viruses of swine, human or avian origin. Today, influenza is a common infection of pigs worldwide, sometimes causing severe respiratory disease in non-immune animals. Infection is maintained in endemic cycles without clear seasonality. Currently, H1N1, H1N2 and H3N2 are the predominant subtypes of swine influenza viruses (SIVs) worldwide, but other virus subtypes have also been isolated occasionally from pigs in some parts of the world, e.g. H9N2 and H5N1.
Following the detection of human cases of influenza H3N2v virus, this virus has subsequently been detected in pigs in several US states designated H3N2pM virus. With respect to significance for the health of pigs of the occurrence of H3N2v virus, if the pig population is completely naïve, it can be assumed that the significance of infection with H3N2pM virus will be comparable to infection of a naïve population with other swine influenza viruses (SIV), as happened in the past in Europe or US.
In field infections with H3N2pM in pigs in the USA (agricultural fairs) a subclinical course was very common, and when clinical signs were observed (coughing, fever), they were generally mild, with low morbidity and no mortality.
Pathogenicity studies in naive pigs experimentally inoculated with H3N2v show that the infection is purely of respiratory nature and shows a relatively mild course with fever, coughing and inappetence similar to that of other SIVs currently circulating in the swine population. Thus the impact of H3N2pM, if introduced, on the health of the European pigs is not expected to differ significantly from the impact of already circulating, endemic SIVs.
With respect to the risk of introduction of H3N2v in EU, the likelihood of a possible introduction of H3N2v virus into EU pig holdings by movement of live pigs according to EU animal health import legislations was assessed qualitatively and considered to be low. Moreover, in particular, the likelihood of pig holdings in the EU being exposed to H3N2v virus by persons working in the pig sector or regularly visiting pig fairs in the USA was judged to be low, whereas the likelihood was considered negligible for other persons travelling from the USA. Efficient separation of imported pigs for 30 days upon the farmers‘ decision would reduce the likelihood of exposure of EU pigs to a negligible level.
However, given that the a first holding has become infected, the likelihood of spread of H3N2pM from pigs of that holding to pigs in a second holding located in the same Member State was expected to be high, assuming frequent movement of pigs between holdings and a high likelihood for pigs in a second holding to be susceptible.
With respect to the diagnostic capabilities to early detect H3N2v incursion in EU, early detection of H3N2pM/H3N2v in the EU is not likely due to the limited current surveillance effort in combination with routine use of diagnostic approaches which are not able to specifically identify this new strain.
Currently applied real time RT-PCRs based on the matrix (M) or the nucleoprotein (NP) gene are capable of detecting all of the influenza A viruses known to be endemic in European pigs plus emergent strains such as rH3N2p from North America. However, neither these tests nor real time RTPCRs based on H3 or N2 genes are able to specifically identify the H3N2pM as being different from European strains. The panel of serological reagents for conventional typing will reliably type all H3N2 strains and the H3N2pM will raise a different reactivity profile in such assays, due to its antigenic differences when compared to European H3N2 SIVs.
Only by combining currently applied diagnostic approaches with gene sequencing will it be possible to identify H3N2pM should it occur in Europe either in pigs or in humans. All of these diagnostic approaches are relevant to the timely identification of variant viruses or new strains that may appear in European pigs. This combination is not done on a routine basis and there is no official surveillance for SIV as this is not a listed disease. It is recommended to reinforce the monitoring of influenza strains circulating in pigs in EU.
With respect to the implications and consequences of the possible evolution of H3N2v virus on pig health such as clinical manifestation and transmission between pigs, it is considered likely that the H3N2pM virus would have the potential to cause disease, to spread and to become endemic. As seen with other SIVs, host selection pressures may drive genetic evolution of the strain, especially in the gene segments encoding the external glycoproteins (HA and NA).
According to the risk assessment developed, given that a first holding has become infected, the likelihood of spread of H3N2pM virus to second holdings was expected to be high assuming a frequent movement of pigs between holdings of the same Member State, and there is a high likelihood for pigs in a second holding to be susceptible.
With respect to the risk that animals from a herd which was infected with influenza A (H3N2v) virus spreads the virus after the last clinical signs of disease have been observed, it is concluded that, independent of whether clinical signs are present or not, the virus excretion in individual pigs may last up to 7 days post infection. Furthermore, clinical signs, when present, do not entirely cover the period of virus excretion. Consequently, an absence of clinical signs cannot be used as evidence of absence of virus excretion. At farm level SIV infections can be maintained with a continuous introduction of susceptible pigs. Therefore, the risk of spread from holdings can remain high for an extended period of time even after cessation of clinical signs. This takes place particularly when susceptible pigs continuously enter the fattening unit.
With respect to the possibility, efficacy and efficiency of vaccination in pigs, using the existing vaccines or newly developed vaccines against influenza A(H3N2v) virus, immunity resulting from vaccination with commercially available European SIV vaccines is expected to provide no or only a low level of cross-protection against infection with the H3N2pM influenza viruses, whereas vaccines based on North American swine H3N2 viruses would offer superior protection. Such vaccines may significantly reduce H3N2pM replication in the lungs of vaccinated animals. However, voluntary vaccination of pigs with existing vaccines has not succeeded in halting the circulation of SIV in the swine population and this limitation is also considered valid for H3N2pM.
According to the available data, H3N2pM/H3N2v is not present in the European swine population and no measures are needed with regard to vaccination. If such a virus should enter Europe and spread in the pig population, then use of US licensed vaccines based on closely related H3N2 strains could be useful.
With respect to the use of vaccines in relation to the possible evolution of variants of influenza viruses posing a risk to public and animal health, vaccination might increase antigenic drift of circulating influenza strains, and newly appearing variant might not be neutralized by vaccine-induced antibodies. However, based on current knowledge there is no indication that the latter has happened with the use of the available SIV vaccines in the European pig population. Furthermore, based on the likely divergent evolution of H3N2pM in pigs compared to humans, it is unlikely that virus with increased transmissibility to humans would evolve.
With respect to the most important factors to be monitored that would suggest a risk for the emergence of a new pandemic influenza strain from the influenza A(H3N2v) virus, the new influenza strains emerge through natural reassortment and/or mutations and past experience has shown that reassortment events involving inter-species transmission are necessary steps in the evolution of new pandemic strains. However, it is not always clear in which species these events occur. Monitoring for reassortant viruses should therefore include as important target species both pigs and poultry. Several molecular markers in influenza virus genes have been reported to be associated with biological properties related to virulence and transmission. However, these associations have been inconsistent between strains and virulence traits appear to be polygenic.
Currently, the number and type of mutations, as well as the genetic constellation that would be needed for efficient human-to-human transmission of H3N2v is unknown.
It is currently not possible to predict which changes (mutations or reassortments) within the H3N2v could enable it become a new pandemic influenza virus. Hence it is not possible to set up a system to monitor “the most important factors (…) that would suggest a risk for the emergence of a new pandemic influenza strain from the influenza A (H3N2v)”.
