Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Commercial ELISAS are available

• Commercial diagnostic kits available in Europe

  Commercial ELISAS are available. Antigen ELISAs are not swine-specific. They can be used for all influenza A viruses. The antibody ELISA is swine-specific.

• Diagnostic kits validated by International, European or National Standards

  There are kits validated by the National or International standards

  GAP

  It is not fully clear to us what is meant by the national and international standards?Which validated kits are available?

• Diagnostic method(s) described by International, European or National standards

  Yes, described by the OIE

• Commercial potential for diagnostic kits in Europe

  Whether there is a potential for widespread use of test kits will largely depend on e.g. cost.

• DIVA tests required and/or available

  Not relevant as eradication is not warranted.

  With so many strains of virus it is difficult to see the advantage of knowing whether vaccinated or not and because of other hosts difficult to see how we could ever eradicate

• Opportunities for new developments

  GAP

  The surveillance of the pig populations worldwide has not changed a lot, despite the outbreak of H1N1. The main reason is the lack of logistics to perform extensive surveillance.

• Vaccines availability

• Commercial vaccines availability (globally)

  A variety of vaccines, usually adjuvanted and using endemic strains in the country of use are available .

  Other vaccines such as DNA, sub-unit, recombinant, adenovirus and live vaccines have been tried experimentally but are not commercially available.

• Commercial vaccines authorised in Europe

  Currently following vaccines are available:• Bivalent (H1N1 + H3N2)• Trivalent (H1N1 + H3N2 + H1N2)

• Marker vaccines available worldwide

  Not available and difficult to work out at the present time why we would want them

• Marker vaccines authorised in Europe

  None

• Effectiveness of vaccines / Main shortcomings of current vaccines

  Currently available vaccines for swine seem to be highly efficient and efficacious. Oil-adjuvanted vaccines provide a broader protection than those with other adjuvants.

  As the viruses change all the time it may be important to to review the viruses in each vaccine but at this stage it does not seem warranted to change vaccine virus at a high frequency (e.g. every year), as is done in humans.

• Commercial potential for vaccines in Europe

  Good potential for vaccines but most farmers are aware that if they practice good husbandry the losses from swine flu are usually minimal and may not justify the cost of a vaccination policy

• Regulatory and/or policy challenges to approval

  Probably none

• Commercial feasibility (e.g manufacturing)

  Probably relatively easy as vaccine producers have already the system in operation for standard oil based vaccines but it depends on the type of vaccine and the goal to be reached

• Opportunity for barrier protection

  Probably not as potential for bird and aerosol spread.

• Opportunity for new developments

  Not likely; cost-benefit for farmer is not likely to be good enough to warrant therapy for diseased pigs (+ risk of residues if the pig needs to be slaughtered anyway).

  In humans, it is not clear whether antiviral treatment (i.e. neuraminidase inhibitors) provides significant benefit over symptomatic treatment (Jefferson et al. (2010). Neuraminidase inhibitors for preventing and treating influenza in healthy adults, Cochrane Reviews).

• Pharmaceutical availability

• Current therapy (curative and preventive)

  Supportive therapy only at the moment.

• Future therapy

  Not likely; cost-benefit for farmer is not likely to be good enough to warrant therapy for diseased pigs (+ risk of residues if the pig needs to slaughtered anyway)

• Commercial potential for pharmaceuticals in Europe

  Not likely; cost-benefit for farmer is not likely to be good enough to warrant therapy for diseased pigs (+ risk of residues if the pig needs to slaughtered anyway)

• Regulatory and/or policy challenges to approval

  None

• Commercial feasibility (e.g manufacturing)

  Unknown

• Opportunities for new developments

  Depends on molecular advances

• New developments for diagnostic tests

• Requirements for diagnostics development

  Continual surveillance of the molecular characteristics of the virus as they change by antigenic drift, shift or species transfer. This requires key core funding not dabbling in and out and should be a feature of all EU national laboratories.

• Time to develop new or improved diagnostics

  On-going and annual. Can’t identify a strain if you do not know of its existence so requires sequencing techniques nationally

• Cost of developing new or improved diagnostics and their validation

  Probably expensive but less so if follows standard EU practice or OIE practise based on lead laboratories eg Weybridge, Ghent and Ames

• Research requirements for new or improved diagnostics

  Continual genetic sequencing of virus isolated from new outbreaks where the professional pig practitioners have noticed unusual features

• Technology to determine virus freedom in animals

  As above

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  Main requirement is the continual monitoring of the virus and its zoonotic or reverse zoonotic potential.

• Time to develop new or improved vaccines

  Currently available vaccines for swine seem to be highly efficient and efficacious. Oil-adjuvanted vaccines provide a broader protection than those with other adjuvants.

  At this stage it does not seem warranted to change vaccine virus at a high frequency (e.g. every year), as is done in humans.

• Cost of developing new or improved vaccines and their validation

  Unknown especially if considering new types of vaccine and if administered by other means eg water or aerosol.

• Research requirements for new or improved vaccines

  Continual genetic sequencing of virus isolated from new outbreaks where the professional pig practitioners have noticed unusual features as well as serological monitoring.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  Probably unnecessary unless the disease begins to cause huge mortality in pigs or becomes a major zoonoses and therefore need to limit viral spread from infected pigs which actually would probably be slaughter and rendering

• Time to develop new or improved pharmaceuticals

  Probably not needed

• Cost of developing new or improved pharmaceuticals and their validation

  Unknown

• Research requirements for new or improved pharmaceuticals

  Monitor the clinical disease in pigs which usually at the moment does not require treatment if care and attention is made to feeding and water provision, warmth and bedding etc.

Disease details

• Description and characteristics

• Pathogen

  Swine influenza virus

• Variability of the disease

  Like all influenza viruses, SIV is a genetically unstable virus as it undergoes antigenic “drift” and “shift”. Antigenic drift involves the gradual accumulation of small mutations in the virus genome, especially in the genes encoding HA and/or NA. This may result in subtle antigenic changes, leading to decreased recognition of the virus by the immune system and thus a greater chance for an influenza epidemic. Antigenic shift is a much more dramatic antigenic change and it refers to the introduction of a virus of another HA and/or NA subtype. There are thought to be 2 main mechanisms through which such a shift is generated: the introduction of a novel virus from an animal reservoir or genetic “reassortment”. The latter can occur when 2 different influenza viruses simultaneously infect the same host cell and subsequently mix to form a newly combined virus. An antigenic shift will only occur when the reassortment involves HA and/or NA proteins.

  In Europe, the predominant H1N1 SIVs have an entirely avian genome and were introduced from wild ducks to pigs in 1979. These avian-like H1N1 viruses have established a stable lineage and have been enzootic on the European mainland since 1979. They are currently co-circulating with H3N2 and H1N2 SIVs. The European swine H3N2 viruses have been derived from descendants of the human virus causing the “Hong Kong flu” pandemic in 1968, but their internal genes have been obtained through reassortment with the avian-like H1N1 virus. The dominant H1N2 viruses retained the genotype of these reassortant H3N2 viruses, but they have acquired an H1 gene through reassortment with a human H1N1 virus from the early 1980s. All 3 subtypes are enzootic in regions of Europe with a high swine density. H1N2 viruses that are the result of a reassortment between European swine H1N1 and H3N2 viruses, have been reported in Denmark and sporadically in other countries, but they are less important.

  In North America, the “classical” swine H1N1 virus, which is a descendant of the 1918 human “Spanish flu” pandemic virus, was the dominant cause of influenza until the late 1990s. H3N2 viruses have only become widespread since 1998. The predominant H3N2 viruses were so-called triple reassortants with genes of classical swine, avian and human origin. These viruses further reassorted with classical swine H1N1 viruses, leading to H1N2 and reassortant H1N1 viruses. Like in Europe, all of the currently circulating viruses contain a genetically similar constellation of internal genes, but have different surface glycoproteins. H1N1 and H1N2 viruses with a human-like HA and/or NA were recently also isolated.

  Most of the European SIVs also circulate in Asia, but there are several lineages that are only isolated from Asia.

  SIV circulates year-round. SI occurred most frequently during late fall and early winter but because swine production has increasingly been conducted in total confinement, the seasonal pattern of disease has become less prominent

• Stability of the agent/pathogen in the environment

  SIV is an enveloped virus and therefore susceptible to many chemical and physical agents. Its stability in the environment is low. It survives better in the colder months

• Species involved

• Animal infected/carrier/disease

  Pigs are infected with swine influenza

• Human infected/disease

  It has long been known that SIVs sporadically jump to humans. There are some 70 documented cases of swine flu in humans since 1958. Most of these people had close contact with pigs and the human disease was usually clinically similar to disease caused by infections with human influenza viruses. A few cases were fatal, but these were mainly in persons with underlying medical conditions.

  GAP

  What factors determine whether an SIV will jump from pig to human is largely unknown. Moreover, transmission of SIVs to a human being per se is not sufficient to result in a pandemic. So far, most SIVs that are transmitted from pig to human did not become established in the human population. Recent evidence clearly shows that the species barrier for an SIV to jump to humans is much stronger than previously suspected.

• Vector cyclical/non-cyclical

  No vectors

• Reservoir (animal, environment)

  Natural reservoir is aquatic birds.Influenza genes from other species other than birds can also become available.

• Description of infection & disease in natural hosts

• Transmissibility

  Some strains are easily transmitted and adapted to pigs. Some are found only occasionally and then die out from the population. Under normal circumstances in a pig unit highly transmissible with all the pigs succumbing to the infection at the same time and recovering at the same time.

• Pathogenic life cycle stages

  Upon infection, SIV replicates in the entire respiratory tract. Clinical signs result from direct respiratory cell damage by the virus and, most importantly, from an extensive production of pro-inflammatory cytokines during the very acute stage of infection. Besides being involved in the severity of disease, the cytokines also exert a strong antiviral and immunostimulating effect. An infection with SIV induces a rapid and efficient immune response, which results in complete elimination of the virus within a week and a solid protection against reinfection.

• Signs/Morbidity

  In many cases the disease may be sub-clinical due to previous exposure/immunity but in most cases there is a sudden onset.

  Respiratory signs: Clinical signs result from direct respiratory cell damage by the virus and, most importantly, from an extensive production of pro-inflammatory cytokines during the very acute stage of infection. Clinical signs are very similar to the symptoms observed in humans and include a rapid onset of high fever, dullness, loss of appetite, laboured abdominal breathing and coughing. A considerable weight loss can be observed. Morbidity is high (even up to 100%), but mortality is usually low (<1%) unless in very young animals and/or when there are concurrent infections. Recovery generally occurs within 7 to 10 days and is as sudden as the onset of disease

• Incubation period

  Usually 2-3 days

• Mortality

  Often nil- 1% unless accompanied by inter-current disease and secondary bacterial infection.

• Shedding kinetic patterns

  Virus is shed from the respiratory tract over the first 1-7 days post infection by coughing and sneezing and nose to nose contact.

• Mechanism of pathogenicity

  Upon infection, SIV replicates primarily in the respiratory tract. Virus replication is detected in epithelial cells of the nasal mucosa, tonsils, trachea, lungs and associated lymph nodes. Virus detection at extra-respiratory sites has been largely unsuccessful.

  Clinical signs result from direct respiratory cell damage by the virus and, most importantly, from an extensive production of pro-inflammatory cytokines during the very acute stage of infection. The extent of cytokine production and, subsequently, the severity of illness seemed to be determined by the amount of virus that reaches the deeper airways and the resulting production of infectious virus. Besides being involved in the severity of disease, the cytokines also exert a strong antiviral and immunostimulating effect and are likely to contribute to the potent specific immune response to SIV.

• Zoonotic potential

• Reported incidence in humans

  Approximately 70 proven cases of SI have been reported in humans since 1958. Most of these people had occupational contact with pigs. None of the SIVs was able to transmit from human-to-human. Serological data suggest a higher frequency of infection, especially in pig farmers and veterinarians

• Risk of occurence in humans, populations at risk, specific risk factors

  A large body of evidence clearly demonstrates that transmission of SIVs to humans can occur.

  It is important to mention that transmission of SIVs to a human being per se is not sufficient to result in a pandemic. So far, most SIVs that are transmitted from pig to human did not become established in the human population. However, the novel 2009 H1N1 pandemic virus clearly obtained the capacity for human-to-human spread and did become established in the human population

  GAP

  What factors (viral and/or environmental) make SIV “fit” to be transmitted to humans is not yet clear.Furthermore, it is unclear why certain SIV, like the novel 2009 H1N1 pandemic virus, subsequently obtain the capacity for human-to-human spread.

• Symptoms described in humans

  Mainly subclinical. In case clinical signs occur, they are the same as for normal seasonal human influenza

• Estimated level of under-reporting in humans

  Probably considerable as the connection between pigs and humans not really understood by population in general and a pig farmer is not likely to report.

• Likelihood of spread in humans

  Possible in the case of the 2009 virus H1N1 as already in the human population.

  NB! nH1N1 is considered a human influenza virus

  GAP

  The likelihood of spread for an SIV in the human population is rare (see above). An SIV needs considerable changes to become adapted to humans. What changes are required, when they occur and how frequent they occur is largely unknown.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  The disease is primarily pig to pig transmitted and therefore no real control except for standard biosecurity. Impossible to prevent bird access on most units especially outdoors and aerosol spread is always a possibility if the neighbouring unit is only 1 km away.

• Endangered wild species affected or not (estimation for Europe / worldwide)

  No

• Slaughter necessity according to EU rules or other regions

  No, unless severe secondary infection eg pleurisy produces a welfare case.

• Geographical distribution and spread

• Current occurence/distribution

  Influenza A viruses are enzootic in the swine population worldwide. Most SIVs are a result of genetic reassortment and they contain a mix of human and/or avian and/or swine virus genes. Pigs have been shown to be susceptible to influenza A viruses of a wide range of H and N subtypes, but only H1N1, H1N2 and H3N2 viruses have maintained themselves in the swine population. The swine viruses differ from their human counterparts at the antigenic and genetic level, because they followed a different evolutionary course after their introduction in pigs. The origin and nature of SIVs also differ on different continents (see above).

• Epizootic/endemic- if epidemic frequency of outbreaks

  Usually endemic, epizootic only when new strain appears and very soon this becomes endemic.

• Seasonality

  SIV circulates year-round. In the past, SI occurred most frequently during late fall and early winter. However, because swine production has increasingly been conducted in total confinement, the seasonal pattern of disease has become less prominent.

• Speed of spatial spread during an outbreak

  Very rapid, nearly all pigs are incubating the disease at the same time.

• Transboundary potential of the disease

  Will spread across all boundaries.

• Route of Transmission

• Usual mode of transmission (introduction, means of spread)

  Usually, nose to nose transmission and possibly also via aerosols in the buildings.

• Occasional mode of transmission

  Possibly people, material and/or organic matter

• Conditions that favour spread

  Large units , with high proportion of young animals.

• Detection and Immune response to infection

• Mechanism of host response

  An infection with SIV induces a rapid and efficient immune response, which results in complete elimination of the virus within a week and a solid protection against reinfection. The specific immune response to SIV includes the production of antibodies in the circulation and at the mucosae of the respiratory tract, as well as a cell-mediated immune (CMI) response. Antibodies are produced to all the major viral proteins. Antibodies to the surface glycoproteins, HA and NA, are associated with resistance to infection, whereas antibodies to the conserved internal antigens, M and NP, are not protective. While anti-NA antibodies hamper the release of newly formed virus from infected cells, only antibodies to the globular head region of the HA can neutralize the virus and thus prevent an infection. Cytotoxic T lymphocytes (CTLs) are mainly directed to the internal NP and M proteins, which are highly conserved between influenza viruses. CTLs mainly play a role in virus clearance and recovery from illness. The CTL response may confer a more broad-spectrum protection, but it must be said that its protective capacity has never been demonstrated in swine.

• Immunological basis of diagnosis

  Usually, the haemagglutination inhibition tests are used

• Main means of prevention, detection and control

• Sanitary measures

  Usual biosecurity probably not very effective. A ban on pig movements may help. Removal of all organic matter on lorries followed by proper disinfection is essential.

• Mechanical and biological control

  Usual control is through vaccination in those countries that have vaccination in other countries the recovered pigs have usually a lifelong immunity but not necessarily to other strains.

• Diagnostic tools

  Clinical signs, post-mortem examination, and histopathology especially with immuno-histochemistry. Virus isolation is extremely important to provide the starting point for strain typing and genetic analysis which is the only way to improve diagnostics and vaccination. Virus isolation is usually in eggs, but occasionally strains are found which do not grow in eggs and tissue cell lines are used. The haemagglutination test is also used to identify the virus, haemagglutination inhibition (HI) can be used for typing as can the fluorescent antibody test. PCR reactions are now widely used. Serological testing relies on the HI test. Other tests have been used but are not commonly carried out by labs with the exception of commercial ELISA kits. Sensitivity and specificity of the ELISA kits are doubtful

• Vaccines

  Adjuvanted vaccines are used in Europe Currently following vaccines are available:• Bivalent (H1N1 + H3N2)• Trivalent (H1N1 + H3N2 + H1N2)Other vaccines sub-unit, DNA, recombinant, adenovirus and live virus vaccines have been produced experimentally.

• Therapeutics

  Support therapy and antimicrobial treatment may be necessary if the pigs are severely ill.

• Biosecurity measures effective as a preventive measure

  Restriction of movement, strict hygiene on the farm

• Border/trade/movement control sufficient for control

  Unlikely to have any effect (birds and defaecation do not respect boundaries)

• Prevention tools

  Vaccination

• Surveillance

  Essential to maintain geographical knowledge of virus subtypes and their spread to develop diagnostics and if necessary vaccines.

• Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

  Too many sources of genetic components of the flu viruses to control (ie birds of all sorts ,particularly aquatic birds but also pigs and humans and possibly other mammals. Vaccination is successful to prevent/minimize SI disease; no eradication strategy warranted

• Costs of above measures

  Unknown

• Disease information from the WOAH

• Disease notifiable to the WOAH

  No

• WOAH disease card available

  No

• WOAH Terrestrial Animal Health Code

  No

• WOAH Terrestrial Manual

  http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.08.08_SWINE_INFLUENZA.pdf

• Socio-economic impact

• Zoonosis: impact on affected individuals and/or aggregated DALY figures

  In general probably not specific impact. At the moment the 2009 virus is a human virus not a pig virus.

  DALY not specific

• Zoonosis: cost of treatment and control of the disease in humans

  Negligible

• Direct impact (a) on production

  Many SIV infections are subclinical. In case of an outbreak, SIV causes unwanted suffering and diminished welfare for the animals. Consequently, the performance of the animals is significantly reduced. It may require support therapy and possible treatment of secondary infection. Probably loss of 1 week of weight gain. Mostly, no extra mortality unless concurrent disease. Subsequently, an outbreak can cause great distress to individual farmers, may jeopardize international trade and cause economic losses to the pig industry in general.

• Direct impact (b) cost of private and public control measures

  No extra requirements

• Indirect impact

  No indirect impact .The public need to be instructed that there is no risk of contracting the disease form eating pork or pork products.

• Trade implications

• Impact on international trade/exports from the EU

  None

• Impact on EU intra-community trade

  None

• Impact on national trade

  None

• Main perceived obstacles for effective prevention and control

  1. Vaccination is unlikely to provide sterile immunity under field conditions2. High cost of vaccination.

• Main perceived facilitators for effective prevention and control

  The practising veterinarian is the only person who can instigate better biosecurity and disease control. The efforts can be aided by health schemes and retail consortia trying to improve the welfare standards of the finished pigs.

• Links to climate

  Seasonal cycle linked to climate

  No

• Distribution of disease or vector linked to climate

  No association

• Outbreaks linked to extreme weather

  No

• Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

  Not as far as is known as yet

Risk

• Suddenly develops pathogenicity of a natural occurring swine strain for humans. Also important: sudden development of transmissibility in other species

Main critical gaps

• What factors determine whether an SIV will jump from pig to human is largely unknown. Moreover, transmission of SIVs to a human being per se is not sufficient to result in a pandemic. So far, most SIVs that are transmitted from pig to human did not become established in the human population. Recent evidence clearly shows that the species barrier for an SIV to jump to humans is much stronger than previously suspected.

  What factors (viral and/or environmental) make SIV “fit” to be transmitted to humans is not yet clear.

  Furthermore, it is unclear why certain SIV, like the novel 2009 H1N1 pandemic virus, subsequently obtain the capacity for human-to-human spread.

  The likelihood of spread for an SIV in the human population is rare (see above). An SIV needs considerable changes to become adapted to humans. What changes are required, when they occur and how frequent they occur is largely unknown.

  It is not fully clear to us what is meant by the national and international standards?

  Which validated kits are available?

  The surveillance of the pig populations worldwide has not changed a lot, despite the outbreak of H1N1. The main reason is the lack of logistics to perform extensive surveillance.

Conclusion

• At the moment the disease is a self-limiting disease of pigs which causes minimal clinical problems and usually resolves without problems unless there are concurrent or predisposing factors.

Sources of information

• Expert group composition

  Expert group members are included where permission has been given

• Reviewed by

• Date of submission by expert group

• References