Diseases

Avian Influenza

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Control Tools

    • Inability of developing countries to control disease,
    • Nature of virus (antigenic drift, antigenic shift),
    • Natural reservoir host,
    • Increasing demands for outdoor poultry production,
    • Potential of some viruses to change from low to high pathogenic,
    • Lack of sufficient cross protection of different H types,
    • Lack of induction of sterile immunity by vaccination; birds which have been vaccinated may shed the virus while remaining asymptomatic. Effective surveillance and movement controls are critical in a vaccination campaign
    • Lack of fit-for-purpose DIVA tools (and lack of validation of existing tools for HPAI in field conditions) - but in many cases sterile immunity is achieved experimentally
    • Lack of mass applicable easy to administer vaccines; lack of sufficient global influenza vaccine production capacity.
    • High population turn-over rates in industrial poultry production provide constant supplies of fully susceptible hosts
    • Lack of control over live bird markets and backyard poultry raising.
    • Public resistance against mass culling.
    • Economic and trade implications of vaccination policies. Lack of transparency of certain countries.
    • Lack of incentive for industry to develop vaccines with a non vaccination policy in place.
    • Limited insight in trade implications and consistent global coordination.
    • Vaccination may put selection pressures on avian influenza viruses, and might eventually result in the evolution of new strains or variants (but selection pressure might also occur in unvaccinated populations of poultry that survive infection such as domestic ducks).
    • Lack of education and compensation of the farmers

    GAPS

    • Lack of sufficient level and consistency of surveillance, lack of adequate compensation and lack of education of farmers, traders and veterinarians.
    • See above – three main factors; structure and nature of poultry sector (usually rapid uncontrolled growth).

  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    Three types of commercial test kits available: 1) Antibody detection ELISA, 2) Molecular methods and 3) Rapid antigen detection systems based on enzymatic immunoassays or on immunochromatography.

    GAPS
    • Many commercial kitshave unknown efficacy or their efficacy has been evaluated on a limited number of viral strains and sample matrixes.
    • For most of the commercial kits available, lack of validation data on sample matrixes collected from non avian species.

  • Diagnostic kits validated by International, European or National Standards

    Only a single avian influenza antibody test kit is on the register of diagnostic tests certified by the WOAH as fit for purpose (https://www.woah.org/en/what-we-offer/veterinary-products/diagnostic-kits/the-register-of-diagnostic-kits/). Scattered validation data of several commercial tests available in different reference laboratories in EU.

    GAPS
    • Meta-analysis of validation data for test kits.
    • Lack of internationally approved standard reagents to validate diagnostic assays/kits.

  • Commercial potential for diagnostic kits worldwide

    Moderate at best; companies focus on Asian markets

  • DIVA tests required and/or available

    There are several serological DIVA schemes:

    1) Neuraminidase differentiation: Use of a vaccine with a different neuraminidase (N) subtype from the field virus. Antibodies to the N of the field virus serve as an infection marker. This method is labour-intensive and time-consuming, which limits its wider use. It is also problematic when new strains of field virus have different N antigens.

    2) Haemagglutinin-only vaccines: The use of vaccines containing only the haemagglutinin (HA) component (e.g. recombinant or subunit vaccines) allows the use of AGID and NP or matrix protein-based ELISAs to detect infection in vaccinated birds.

    Virus DIVA schemes are based on testing for the presence of acute virus infections in vaccinated flocks by RT-qPCRs. This approach is straightforward and provide information on the subtype and pathotype of the virus.

    Clinical DIVA, i.e. use of non-vaccinated highly susceptible gallinaceous sentinel birds that mix and mingle in a flock vaccinated poultry, could be used for syndromic monitoring of vaccinated flocks. Severe practical problems in sentinel placement, mixing and re-identification in large flocks and in waterfowl holdings. In addition, the use of fully susceptible unvaccinated sentinels can increase the risk of flock infection.

    GAPS

    • Better DIVA tests are required.
    • Validity of DIVA for HPAI only partially assessed under field conditions; validity of other methods of assessing infectious status of flocks such as virological testing of routine mortalities needs to be further assessedin the field.
    • Validation of environmental sampling methods and associated protocols for vaccinated flocks are needed in the field.

  • Vaccines availability

  • Commercial vaccines availability (globally)

    H5, H7, H9 poultry vaccines are available. Vaccination of wild birds is not feasible yet. There are different types of vaccines commercially available at present. Inactivated full virus vaccines, recombinant inactivated vector vaccines and recombinant live vector vaccines (fowl pox, herpesvirus of turkey (HVT) or Newcastle disease virus (NDV) vectors). The latter type of vaccines have been produced by inserting the gene coding for the influenza virus haemagglutinin (H5 or H7 for instance) into a live virus vector (e.g. fowl pox virus, NDV, HVT) and using this recombinant virus to immunise poultry against AI. Recombinant vaccines have been licensed in a number of countries. A prime-boost immunization strategy using a vector vaccine to prime and an inactivated (or another vector vaccine) to boost immunity has been shown to induce a broader immune response and protection even in birds with maternal antibodies.

    GAP

    • Knowledge on the mechanisms of maternally-derived antibody interference on the different types of vaccines.

  • Marker vaccines available worldwide

    In principle, yes. DIVA principle with different “N” types. In case of recombinant vaccines expressing only H or H and N of AIV,ELISA test targeting detection of antibodies against for example the virus nucleoprotein can indicate exposure to field infection. Studies for DIVA using sentinel birds is available but information is limited.

    GAP

    • Field studies evaluating the DIVA principle using new recombinant vaccines in practise and larger herds.

  • Effectiveness of vaccines / Main shortcomings of current vaccines

    International organisations recommend that vaccines used for AI control must be of high quality and that they should meet international standards and guidelines. Regarding vaccine efficacy, these guidelines require protection against disease and mortality as well as reduction in levels of virus shedding when compared to unvaccinated birds.

    GAPS

    • Vaccine efficacy is poorly known for poultry species other than chickens. i.e. Turkeys, ducks and geese.
    • Knowledge on vaccine efficacy to stop sustained transmission in vaccinated flocks (for all poultry species) and duration of immunity.
    • Not well defined correlates of protection, particularly for recombinant live vector vaccines.
    • Lack of mass application procedures.

  • Commercial potential for vaccines

    Depends on disease evolution and willingness to vaccinate, epidemiological situation, and value of individual animals (rare captive birds in zoos & hobby holdings) and the cost of compliance programs. The global spread of H5Nx HPAI has changed the perception about the use of vaccination to aid prevention and control of HPAI in poultry. Vaccination has been implemented or is being considered by several countries globally, including some countries in Europe.

  • Regulatory and/or policy challenges to approval

    GAP

    • Need for rapid approval of new seed strains for production.

  • Commercial feasibility (e.g manufacturing)

    Adequate

  • Opportunity for barrier protection

    Yes.

  • Pharmaceutical availability

  • Current therapy (curative and preventive)

    None. Antivirals (Tamiflu & Relenza) are effective in poultry but their use is prohibited due to the risk of antimicrobial resistance (AMR) and hazard thereof for human.

    GAP

    • Not applicable at present stage, however, any therapy should be adapted to the provision in the relevant legislation.

  • Future therapy

    None anticipated in the near future. In the longer term virus specific antiviral may be a possibility. Only drugs not for use in human can be considered.

  • Commercial potential for pharmaceuticals

    None.

    GAP

    • Any scope for siRNA or other methods to increase resistance of poultry to infection and disease?

  • Regulatory and/or policy challenges to approval

    Not applicable.

    GAPS

    • Resistant poultry

  • Commercial feasibility (e.g manufacturing)

    Not applicable.

  • New developments for diagnostic tests

  • Requirements for diagnostics development

    Tests are needed that are easy to use, cheap, usable on farm and applicable to mass screening. Existing technologies based on nucleic acid amplification work relatively well if properly controlled.

    GAP

    • Risks of the use of pen site assays leading to concealing of outbreaks must be weighed against higher costs (but also higher sensitivity) of laboratory-directed diagnosis.

  • Time to develop new or improved diagnostics

    Unknown.

  • Cost of developing new or improved diagnostics and their validation

    Variable.

  • Research requirements for new or improved diagnostics

    Development of pen site tests and alternatives for the simple diagnosis of AI.

    Rapid ELISA/LFD tests still valid as flock tests if performed on dead birds with H5N1 HPAI. However, negative results do not rule out an influenza A infection and other laboratory based testing pipelines should be used.

    GAPS

    Continuous need to improve and validate diagnostic tests:

    • Lack of diagnostic tools that provide consistent, optimal results in any setting and for routine use
    • Rapid molecular tests not easily affected by genetic mutations
    • Sustained characterization of new isolates to assure that current tests will have optimal sensitivity and specificity.
    • Improved virus isolation tools (genetically tailored cell lines, stabilizing transport media)
    • Rapid and improved phenotyping tools to rapidly characterize key properties such as virulence, infectivity, host-range and transmissibility
    • Laboratory protocols for detection of less common influenza viruses or viruses with little economic consequences for the poultry and pig sectors, enabling to screen also for potentially pandemic viruses.
    • Need for whole genome sequencing protocols able to characterize viruses in sample with low viral concentration (e.g. environmental samples, vaccinated flocks)
    • Bioinformatic tools to monitor the influenza virus evolution and promptly identify mutations associated with mammalian adaptation, virulence, resistance toward antiviral drugs or evasion from the host’s antiviral response or vaccine induced immunity

  • Technology to determine virus freedom in animals

    GAPS

    • Improved diagnostic tests with higher specificity and sensitivity especially for the early stages of infection.
    • Assess the use of virological testing (not just relying on serology especially when dealing with rapidly fatal disease).

  • New developments for vaccines

  • Requirements for vaccines development / main characteristics for improved vaccines

    The requirements are for multiple strain coverage, easy to apply (mass vaccination), single dose, cheap, marker vaccines, induction and persistence of shedding of virus avoided, efficacious in birds with maternal antibodies. Efficacious to stop sustained transmission.

    GAPS
    • It is envisaged that evaluation of MS dossier will not be appropriate in response to an emergency situation.
    • The mechanisms of maternally-derived antibody (MDA; passive immunity) interference on the different types of vaccines need to be better understood. For vector vaccines, both the anti-vector and the anti-AI insert MDA effects need to be studied.
    • For vector vaccines, the effect of anti-vector active immunity may also need to be considered especially in case of emergency vaccination of multi-age bird holdings.
    • Other vectors – e.g. salmonella; antigens produced in plants, live-attenuated viruses (bat influenza-constructs).

  • Time to develop new or improved vaccines

    Variable but usually quite long (at least 5 years). Depends on vaccine type, product profile, priorities, registration authorities’ requirements and funding possibilities.

  • Cost of developing new or improved vaccines and their validation

    Variable. The proof of concept may be a couple of hundred thousand euros but the full development is several millions euros.

  • Research requirements for new or improved vaccines

    Development of recombinant vaccines, sub unit vaccines and possible DNA/RNA vaccines.

    • Live vaccines would enable improved methods of application such as spray or drinking water would provide major advantages.

    • The use of live vaccines which are genetically engineered to avoid the potential disadvantages of reversion to virulence, reassortment with field strains or resulting in vaccine induced respiratory disease would be important.

    • Use of reverse genetics to generate reassortment marker vaccines.

    • Develop live vaccine viruses which only undergo partial replication in the host in order to stimulate an immune response but which cannot progress to full replication of the virus. Need to use replication deficient strains which in turn requires a detailed understanding of the AI virus replication mechanisms and of the functional genetic of the virus Systems

    • Hatchery vaccination (In ovo, SC or spray)

    • Cost-effective vaccines

    GAP
    • Costs relating to the research and development of some types of vaccines in the face of a potentially limited market.

  • New developments for pharmaceuticals

  • Requirements for pharmaceuticals development

    Not applicable at present.

  • Time to develop new or improved pharmaceuticals

    Not applicable at present.

  • Cost of developing new or improved pharmaceuticals and their validation

    Not applicable at present

  • Research requirements for new or improved pharmaceuticals

    Not applicable at present.

    GAP

    • Not applicable at present stage, however, any therapy should be adapted to the provision in the relevant legislation.

Disease details

  • Description and characteristics

  • Pathogen

    The infection is caused by virus strains from the Orthomyxoviridae family, genus Influenzavirus, type A. Influenza A viruses (IAV) are enveloped, spherical-pleomorphic viruses with a diameter of 80-120 nm. The genome, single-stranded negative sense RNA, is segmented and encapsidated in eight genome segments which code for up to 11 proteins. The nucleotide sequence as well as the antigenic properties of the hemagglutinin (H or HA) and neuraminidase (N or NA) surface glycoproteins classify type A influenza viruses into 18 hemagglutinin (H1 to H18) and 11 neuraminidase (N1 to N11) subtypes. IAV infect a broad range of avian and mammalian species. Recently, IAV-like viruses were also detected in bats (H17N10, H18N11). Clinical symptoms induced after infection vary considerably according to both viral and host properties. IAV circulating in avian hosts are also referred to as avian influenza viruses (AIV). Aquatic wild birds constitute the reservoir of all AIV subtypes (H1-16/N1-9) known to date. AIV virus is capable of infecting non-reservoir avian species, too, and occasionally is transmitted even to mammalian hosts.

  • Variability of the disease

    In addition to subtype classification AIV are distinguished by their pathogenic potential in chickens. Highly pathogenic AIV (HPAIV) induces high mortality rates in gallinaceous poultry while strains of low pathogenicity (LPAIV) induce significantly milder courses or even asymptomatic infections. An intravenous pathogenicity index (IVPI) is used to distinguish the pathotypes. Alternatively, the deduced amino acid sequence at the endoproteolytic cleavage site of the HA protein can be used as a surrogate marker of pathogenicity. To date, all naturally occurring HPAIV are representatives of subtypes H5 and H7. However, the majority of H5/H7 circulating is of the LP type.

    IAV in general have considerable genetic flexibility through point mutations, which accumulate due to (i) an intrinsically high mutation rate of these viruses (genetic drift, creating a quasispecies-like cloud of genetically closely related but not identical individual virions) and (ii) through exchange of whole genome segments (genetic shift) during co-infection of a single host cell with IAV of the same or different subtypes (reassortment). HPAIV arise by de novo mutation, probably in gallinaceous poultry, from LP precursor viruses of subtype H5 and H7 which are maintained in the natural host reservoir.

    GAPS

    • Knowledge regarding virus-host interactions, and on factors that affect disease pathogenesis, to allow more effective infection control, such as:
    • Genetic variations and phenotypic traits of the virus that determine virulence, host specificity and zoonotic potential.
    • Mechanisms of virus adaptation to different host species.
    • Factors that determine tissue tropism of the virus.
    • Molecular mechanisms of gene re-assortment between virus subtypes (“genome compatibility”).
    • Mechanisms of clinical resistance in different host species (e.g. anserifrom vs gallinaceous poultry).
    • Factors that influence virus excretion kinetics (e.g., is there a kind of carrier state/prolonged virus excretion in certain species or immune compromised animals?).
    • Differences in pathogen interaction between field and laboratory studies (e.g. role of age component, co-infections, adverse environmental conditions [tropical climates])
    • How are subtypes that are rare in aquatic birds being maintained in nature? Additional unsampled reservoir species?

  • Stability of the agent/pathogen in the environment

    Infectivity of AIV depends on the integrity of their lipid envelope; therefore they are sensitive to most detergents and disinfectants, and are inactivated by heating and drying. The pathogen can be inactivated at 56°C/3 hours or 60°C/30 min or 72°C/1min, by acid pH, oxidising agents, sodium dodecyl sulphate, lipid solvents, ß-propiolactone, formalin and iodine compounds. However, depending on environmental conditions, especially temperature and humidity, AIV infectivity may persist in soil, faeces, and surface waters for varying amounts of time. In lake water at 4°C infectivity remains stable over many months. Freezing does not destroy infectivity, but repeated freeze-thawing cycles do.

    GAPS

    • What genetic and phenotypic factors influence improved survival at various temperatures (certain H5N1 viruses survive for longer at 30 and 37 degrees)?
    • What is the survival at 30-35 degrees in a range of substrates (water, faeces, in or on feathers etc; this represents the sorts of temperatures experienced in much of the tropics where H5N1 viruses persist)
    • What is the role of environmentally deposited AIV (e.g. in surface water or in sediments of shallow lakes) in sustained circulation of AIV in the natural host reservoir?

  • Species involved

  • Animal infected/carrier/disease

    AIV infections are widely distributed in aquatic wild bird populations. The majority of infections is transient and clinically mild, if not asymptomatic, although an impact of infection e.g. on migration habits has been described. There is no evidence as yet for a carrier status or persistent infections. Fecal-oral transmission chains dominate in wild birds. The environment (surface water, sediments) probably acts as an important factor of virus perpetuation. Incidence of infection tends to follow the annual cycle of the natural hosts and correlates with seasonal production of young, and hence large input of susceptible individuals. Peak values of up to 30% can be observed during autumn migration of aquatic wild birds in the Northern hemisphere. Accidental AIV infections of domestic poultry population from wild birds occur occasionally given exposure of poultry to virus-contaminated fomites (e.g., higher risk when domestic birds are kept outdoors). Nevertheless, infection with some wild bird-derived subtypes may become enzootic in poultry; the most important enzootic LPAI infection currently is by the LPAI H9N2 subtype that affects poultry holdings from North Africa to Far East Asia. and causes severe respiratory problems together with other agents.

    GAPS

    • Given the acute nature of infection, how is IAV maintained in a flyway perspective? What is the migratory connectivity between East Asian and European waterfowl, and how does that relate to spatial spread of HPAIV.
    • Factors or co-factors that contribute to the pathogenicity and the enzootic nature of H9N2 infection in field conditions.

  • Human infected/disease

    Yes. Principal zoonotic potential exists, risk of infection mainly related to close direct contact with infected birds or contaminated poultry products. Exposure to high doses of virus probably required. In general, a rare event so far as regards overt clinical human disease. No evidence of sustained human to human transmission for the current H5 and H7 strains.

    GAPS
    • Relation of virus exposure dose and clinical/immunological effects unknown
    • Predisposing factors of human susceptibility on viral and host sides.
    • Assess the rate of transmission;why is there an apparent difference between H5 and H7 viruses?
    • Zoonotic risk posed by clinically normal poultry infected with LPAI H7N9 – need tools to efficiently screen poultry populations for asympotmativ zoonotic AIV infections.

  • Vector cyclical/non-cyclical

    None identified.

  • Reservoir (animal, environment)

    LPAIV: Aquatic wild birds and domestic waterfowl are the primary reservoirs for AIV, serving as a source of infection for other birds within their migratory pathway.

    LPAIV H9N2: Gallinaceous poultry

    HPAIV: Poultry (in particular domestic waterfowl).

    GAPS

    • Mode of “environmental” transmissions unknown (virus free floating in surface water, contact with sedimented virus etc.)
    • Frequency, mode & risk of contacts between wild birds and poultry
    • Definition of a “risk contact”
    • What is the role of virus on feathers and is uropygeal gland secretion protective?
    • Role of rapid turnover of poultry populations and of poultry vaccination in perpetuating LPAIV and HPAIV circulation and driving virus evolution.
    • What is the migratory connectivity between wild reservoir populations in Eurasia.

  • Description of infection & disease in natural hosts

  • Transmissibility

    Sources of the virus are mainly faeces and respiratory secretions. Transmission is via contact with infected birds or contaminated fomites (surface water!). . Transmissibility of AIV varies among virus subtypes and pathotypes (LPAI or HPAI) and poultry species. Transmission being faster and to a higher extend between turkeys or between ducks compared to chickens. Oral transmission to mammals possible; other routes of mammalian infection possible (conjunctival transmission). Transmission between cattle, particularly dairy, of H5N1 HPAI appear to be associated with transmission via the udder during the milking.

    In case of AIV outbreaks on poultry holdings, the mechanisms of transmission from infected to susceptible farms are not fully understood, since collected data during epidemics has not been sufficient to identify specific routes. In the absence of animal movements, several possible routes of transmission have been identified including airborne spread. There are however identified factors that explain the risk of transmission between farms are: 1) farm density, with high transmission risk observed in farm dense areas, 2) poultry species (higher transmission between turkey or duck farms than chicken farms), 3) farm size, with the risk of transmission being higher in large farms.

    In vaccinated poultry flocks, when vaccination is not effective and infections enters the flock, the transmission kenetics will vary depending on the level of flock immunity at the moment of infection and the virus transmissibility. Transmission in vaccinated and infected flocks is expected to be slower and to a lower extend than transmission in unvaccinated flocks.

    GAPS

    Knowledge regarding virus-host interactions, and on factors that affect virus excretion and spread, to allow more effective infection control, such as:

    • Genetic variations and phenotypic traits of the virus that determine virulence, host specificity and zoonotic potential.
    • Mechanisms of virus adaptation to different host species.
    • Factors that determine tissue tropism of the virus.
    • Differences in pathogen interaction between field and laboratory studies (e.g. role of age component, co-infections)
    • Knowledge on correlates of transmission, such as virus shedding titers and kinetics of shedding in relation to transmission.
    • Possible contribution of stamping out methods on between farm transmission as a result of the release of virus into the environment (e.g. aerosolization of virus)
    • Modes of farm-to-farm transmission in case of outbreaks.
    • Factors driving persistence and transmissibility of LPAI and HPAI virus infections in farms from endemic regions.
    • Transmission kenetics of LPAI and HPAI viruses in vaccinated poultry flocks.

  • Pathogenic life cycle stages

    Transmission from acutely infected individuals or contaminated fomites to susceptible hosts. Infectious period of HPAI virus infections in turkeys and chickens is shorter (on average < 5 days) than that in ducks and geese (> 5 days). Infectious periods for LPAI infections are longer thatn HPAI infections regardless of the poultry species. No evidence as yet for persistent infections/carrier state.

    GAPS
    • Mechanisms of adaptation of LPAI to poultry; what predisposes an LPAIV to replicate in gallinaceous poultry
    • Mechanisms of adaptation of HPAI to different avian (domestic and wild) and mammal species.
    • Effect of age or production phase (eg. Pullets and layers) on susceptibility and transmission.
    • Can we modulate susceptibility to LPAI via controlling co-morbidities?

  • Signs/Morbidity

    HPAIV: Symptoms are severe depression, inappetence; drastic decline in egg production; facial oedema with swollen and cyanotic combs and wattles; sudden deaths (mortality can reach 100%). Occasionally petechial haemorrhages on internal membrane surfaces; Lesions in chickens (not pathognonomic):

    • Lesions may be absent in cases of parachute death
    • Severe congestion of the musculature
    • Dehydration
    • Subcutaneous oedema of the head and neck area
    • Nasal and oral cavity discharge
    • Severe congestion of conjunctivae, sometimes with petechiae
    • Excessive mucous exudate in the lumen of the trachea, or severe haemorrhage tracheitis
    • Occasional petechiae on the inside of the sternum, on the serosa and abdominal fat, serosal surfaces and in the body cavity
    • Severe kidney congestion, sometimes with urate deposits in the tubules
    • Haemorrhages and degeneration of the ovary
    • Haemorrhages on the mucosal surface of the proventriculus, particularly at the juncture with the gizzard
    • Haemorrhages and erosions of the gizzard lining
    • Haemorrhagic foci on the lymphoid tissues in the intestinal mucosa
    • Pulmonary oedema and congestion
    • Splenomegaly
    • Pancreatic necrosis

    The lesions in turkeys are similar to those in chickens, but may not be as marked due to a high proportion of hyperacute deaths. Ducks infected with HPAI and excreting the virus, may not show any clinical signs or lesions. In HPAIV infected geese neurologic signs may dominate (atactic movement, myoclonus, forced movements, torticollis, somnolence). Also neurological signs in ducks; corneal opacity in ducks.

    LPAIV: Symptoms in domestic poultry are extremely variable. Clinical signs (inappetence, respiratory distress, reduced production parameters) most frequently observed in turkeys. H9N2 is part of the respiratory disease complex observed in a high proportion of poultry flocks from North Africa to Far East Asia.

    Viral pathotype is not correlated with zoonotic properties and clinical pictures induced in humans: LPAIV H7N9 is highly attenuated in gallinaceous poultry but induces fulminant and often fatal respiratory disease in exposed humans. This hampers identifying suspicious flocks on basis of syndromic surveillance.

    GAPS

    • No pathognomic symptoms or surrogate markers of infection defined.
    • Define trigger points for investigations in different types of flocks including vaccinated flocks.
    • Role of concomitant infections on clinical pictures of LPAIV (H9N2 and H7N9) infections in gallinaceous poultry and of HPAIV in domestic waterfowl.

  • Incubation period

    The incubation period is 1 to 7 days. Can be slightly prolonged depending on viral strain and host species (e.g., in turkeys infected with U.S. HPAIV H5N2 reassortants).

    GAP

    • Evaluate the incubation period in birds vaccinated with different types of vaccine?

  • Mortality

    The “low pathogenic” types may spread clinically silent and remain undetected or cause only mild symptoms and, hence, often escape syndromic surveillance.

    LPAIV-associated mortality in certain conditions, e.g. concomitant infections or adverse environmental conditions, can increase significantly and may reach up to 30% (e.g., H9N2 infection in layers in Asia).

    However, the highly pathogenic forms cause disease that affects multiple internal organs and has a mortality rate that can reach 90-100% often within 72 hours in gallinaceous birds in experimental conditions. Some HPAIV infections in waterfowl can run a much more attenuated course and can be clinically indistinguishable from LPAIV infections.

  • Shedding kinetic patterns

    Following infection virus shedding occurs. Effective infectious period is usually short (1-5 days). Shedding mode (fecal versus oropharyngeal) depends on viral tissue tropism. For poultry, oropharyngeal shedding appears to happen before cloaca shedding and virus concentrations are higher than the concentration observed in cloaca shedding. Transmission experiments showed that most transmission takes place during the first days following infection when mostly oropharyngeal shedding is observed. Vaccination to be fully effective must suppress shedding below the point where it will infect other vaccinated poultry.

    GAPS

    • Virus shedding titers and kinetics of shedding in relation to transmission rates & vaccination status.

  • Mechanism of pathogenicity

    Cellular level: Receptor-bound viruses are taken into the cell by endocytosis. In the low pH environment of the endosome, the viral lipoprotein envelope fuses with the lipid-bilayer of the vesicle releasing viral RNA into the cell cytoplasm from where it is transported into the nucleus. New viral proteins are translated from transcribed messenger RNA (mRNA). New viral RNA is encased in nucleocapsid protein, and together with new matrix protein is then transported to sites at the cell surface where envelope hemagglutinin and neuraminadase components have been incorporated into the cell membrane. Progeny virions are formed and released by budding.

    Host level: Dysfunction of infected cells (e.g. lack of ciliary activitiy of respiratory epithelial cells) will cause local symptoms. Replication of LPAI virus is largely confined to endodermic epithelia, although some strains may go beyond. HPAI virus, in contrast penetrates epithelial borders and will initiate multiple replication cycles systemically, including the central nervous system. Certain isolates interfere with innate immunity.

    GAPS
    • Rate and selection pressure of mutation at the cleavage site. Does the transition from LPAIV to HPAIV usually take place in gallinaceous poultry and what host factors may be predisposing this step?
    • Tissue tropism of LPAIV; why do some strains replicate beyond the basal membranes of respiratory and intestinal tissues (e.g. kidney, adrenals etc.) and what are the mechanisms of pathogenesis in these extra-respiratory/intestinal tissues?

  • Zoonotic potential

  • Reported incidence in humans

    Moderate, unpredictable zoonotic potential exits. See WHO statistics for HPAIV H5N1, and LPAI H7N9.

    GAP
    • Lack of knowledge of true incidence in humans.

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

    Most but not all cases of AIV infection in humans have resulted from close contact with high viral doses from infected poultry or surfaces or products (raw eggs!) contaminated with secretion/excretions from infected birds. Elderly generation may be more susceptible/vulnerable for certain viruses (LPAIV H7N9/China).

    GAP

    • Genetic resistance/susceptibility of humans; mode of exposure when infected humans reported no contacts with poultry.

  • Symptoms described in humans

    Symptoms of avian influenza in humans have ranged from typical human influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to conjunctivitis, pneumonia, severe respiratory diseases leading to acute respiratory distress syndrome, and other severe and life-threatening complications.

    GAP

    • Are humans more susceptible to H7 than H5 HP/LP viruses and if so why?
    • What is the zoonotic potential of H9N2?

  • Estimated level of under-reporting in humans

    Probably low but unknown.

    GAPS:

    • Understanding of the changes of clinical severity (towards less severe symptoms) in human infections, e.g. by HPAIV H5N1 in Egypt or HPAIV H5N6 in SE Asia.
    • Reporting depends on likelihood of hospitalisation and cost of hospital treatment precludes many cases in endemic areas from attending hospital.

  • Likelihood of spread in humans

    The spread of AIV from an infected individual human to another has only been reported very rarely, and has so far been limited, inefficient and unsustained. Efficient or sustainable transmission has not yet been reported in humans.

    GAPS

    • Mechanisms of AIV adaptation to humans.
    • Identification of genetic signature markers that are prognostic of the zoonotic/pandemic potential of the virus.
    • Retrospective epidemiology in exposed human populations to fully evaluate the rate of clinically silent human infections.

  • Impact on animal welfare and biodiversity

  • Both disease and prevention/control measures related

    The effects of HP strains could cause significant suffering in a large number of domestic birds and a wide range of wild bird species. The incidence of respiratory diseases due to LPAI (and especially H9N2 in endemic regions) may certainly have an impact on animal welfare.

    Control measure foresee the culling of infected and suspected flocks in case of HPAIV and in PLAIV infections with subtypes H5 and H7. Culling methods such as CO2 gasing, suffocation by foam etc. may have heavy impact on animal welfare if not practised appropriately.

    GAPS

    • Relative advantages and disadvantages of wide area culling versus other control methods.
    • Incentives for disease reporting.
    • Cost-effective, safe and humane culling methods, in particular for waterfowl.
    • Need to explore alternative control options to culling.

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

    HPAIV H5N1 and also other HPAI viruses can infect, with fatal outcome, a wide range of avian species, many of them endangered. Avian raptor species may be specially threatened due to increased risk of hunting on diseased and weakened prey or by scavenging activities.

    Transmission to mammals (apart from humans) sporadically have occurred and induced fatal disease in several carnivorous and amnivorous species such as tigers, leopards, housecats, dogs, palm civets, stone martens.

  • Slaughter necessity according to EU rules or other regions

    Prohibited slaughtering in case of HPAIV infected poultry, culling and destruction demanded instead (marketing of products prohibited). Yes, for LP H5/H7 infected poultry if culling and destruction is economically/ethically not considered; herds must be virologically negative before transport to slaughterhouses.

    GAPS
    • Risks of virus spread by LPAIV H5/H/ infected flocks that are deemed to be slaughtered.
    • Risk of virus spread by products from slaughtered LPAIV infected flocks.

  • Geographical distribution and spread

  • Current occurence/distribution

    Global. LPAIV strains are found worldwide in the aquatic wild bird reservoir. The most widespread endemic infection with LPAIV in commercial poultry covers the region from North Africa to China/Korea and is caused by different lineages of subtype H9N2. Additional LPAIV endemic infections include the H5N2 LPAI in Mexico and, probably, neighbouring countries. Zoonotic LPAIV H7N9 is endemic in China; the poultry reservoir of this enzootic infection is not fully resolved. Sporadic human infections by H7N9 continue to occur in seasonal waves and are related to virus exposure of the patients in local live poultry markets. Sporadic incursions of LPAIV from the wild bird reservoir are unavoidable due to the reservoir function of wild birds and, hence, are reported repeatedly from all countries with commercial poultry holding activities. Infections with subtypes H5 and H7 (LPAIV) are notifiable to the O.I.E. and prompt mandatory restriction measure.

    HPAI virus infections that arose de novo by mutation from LPAIV precursors of subtypes H5/H7 continue to be reported sporadically from poultry populations in the Americas, Europe, Asia and Australia but at grossly lower rates compared to LPAIV H5/H7. Most of the outbreaks have been eradicated promptly.

    HPAIV H5N1 of Asian origin and its reasserted progeny lineages of subtype H5Nx are enzootic in poultry populations in Asia, Northern and Western Africa. Between 2003 and 2008, HPAIV H5N1 spread epizootically into domestic or wild bird populations in other regions of Asia as well as parts of Europe, the Middle East and Africa. Some countries have eradicated the virus from their domesticated poultry but eradication of HPAIV H5N1 on a global scale is not expected in the short term as pockets of endemic infection, especially in domestic waterfowl, continue to exist in several countries. Frequent reassortment of the Asian origin HPAIV H5N1 with other subtypes circulating in wild birds and/or poultry lead to HPAIV subtypes H5N2, H5N6 and H5N8 n some of them now also enemic in SE Asia. Northern America experienced extensive HPAIV outbreaks in 2014/2015 originating from HPAIV H5N8 incursions via Beringia by migratory wild birds. Reassortment of this virus with resident LPAIV of American descent produced reassortant HPAIV strains H5N1 and H5N2. The latter, in particular, caused a series of outbreaks mainly by lateral spread between poultry holdings. Last cases of HPAIV were reported from North America in June 2015.

    GAPS
    • Persistence and duration of excretion of H5N1 by wild bird species. Can wild birds be reservoirs for HPAI viruses?
    • Relative contribution of factors that lead to persistence of H5NX HPAI and LPAI H9N2 in countries with endemic infection.

  • Epizootic/endemic- if epidemic frequency of outbreaks

    Variable, depending on the effectiveness of the control measures. In Europe the rapid implementation of harsh controls (stand still-culling-C+D) can prevent spread within the domestic populations of birds effectively.

  • Seasonality

    Possible link to bird migration/movement patterns (both LPAIV & HPAIV). HPAIV: Annual shifts in incidence in endemic regions (SE Asia, Egypt) linked to cooler/more humid times of the year or to increased poultry production and trading movements during nation-wide celebrations/holidays (e.g. Tet/Vietnam, Ramadan/Egypt, Indonesia).

  • Speed of spatial spread during an outbreak

    Variable, depending on initial identification and diagnosis and the speed of implementation of effective controls. Can be rapid if migratory wild birds are involved in spread.

    GAP

    • Which factors allow HPAIV to become “mobilized” in migratory wild bird populations?

  • Transboundary potential of the disease

    High. Uncontrolled and illegal trading activities with live poultry and all kinds of poultry products. Spill-over into wild bird population and (secondary) spread with migratory species possible.

    GAP

    • Trade control
    • Efficient wild bird AIV surveillance

  • Route of Transmission

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

    Direct contact with secretions from infected birds, especially faeces, saliva and nasal secretions or contaminated fomites or water is the most common.

    GAPS

    • Role of aerosol or neighbourhood transmission and relative contributions of various routes of transmission.
    • Role of contaminated/infected feathers (H5).

  • Occasional mode of transmission

    Asymptomatically infected aquatic birds may introduce directly or indirectly the virus into flocks.

  • Conditions that favour spread

    Close contact with infected wild species and domesticated birds (co-habitation in free range poultry holdings), dense populations of susceptible species, mixed populations of susceptible poultry (waterfowl and gallinaceous fowl), high population turn-over rates (continuous production of susceptible individuals). Uncontrolled poultry trading movements (including shared machinery, transport vehicles etc.).

    GAP

    • Mode and frequency of contacts between wild birds and poultry.

  • Detection and Immune response to infection

  • Mechanism of host response

    Humoral immune response (antibodies) is protective but is subtype- and even strain-specific (narrow range). Antibodies directed against HA-1 protein confer narrow-range but effective virus neutralization. Antibodies to HA-2 part suspected to be broadly neutralising. Little is known concerning T-cell immunity. Immunology in waterfowl and gallinaceous poultry differs and is not really known very well. Interaction of virus and host on the molecular level not well understood; immune escape mechanisms of virus include interference with innate immunity (NS-1 protein), antigenic drift and antigenic shift (affecting the HA protein).

    Similar questions remain for infections of mammals, particularly for human HPAIV H5N1 infections: immunopathological mechanisms contribute to severity of disease in humans.

    GAPS
    • Understanding of sequence difference of virus-host interactions and factors that impact on immune responses to allow more effective infection control, such as:
    • Insufficient knowledge of many areas of influenza immunology, such as importance of mucosal versus systemic immunity, cellular versus humoral immunity in different species, mechanisms of cross-protection or other/novel mechanisms.
    • Duration of carriage of virus in immunosuppressed or partially immune animals or certain species, particularly during migration.
    • Contribution of immune response to pathogenesis (vaccines).

  • Immunological basis of diagnosis

    Detection of IAV generic and subtype-specific antibodies.

    GAPS
    • High-throughput subtype-specific multiplex serological tools for screening.
    • On-site serological tools (vaccination efficacy control)
    • Validation of serological DIVA in the field.

  • Main means of prevention, detection and control

  • Sanitary measures

    Decrease interface areas of contact between poultry and wild birds, in particular waterfowl. Avoidance of the introduction of birds of unknown disease status into flock. Control of human traffic. Proper cleaning and disinfection procedures. One age group per farm ('all in-all out'). Single species per holding. Compartmentalization.

    Phase 1:

    • Implementation of restriction measures at a farm level
    • Establishment of protection and surveillance zones

    Phase 2: Enlargement of restriction zones (ban of restocking in large areas)

    Phase 3: Implementation of vaccination plan if other measures fail.

    GAPS

    • Which measures on farm offer the best value for money? HACCP algorithms to detect and balance biosecurity gaps.
    • Decision trees for vaccination in endemically infected countries.

  • Mechanical and biological control

    Biosecurity, contact prevention to migratory birds and bridge species, movement control of poultry, eradication of incursions by stamping out eventually combined with vaccination.

    GAP

    Role of bridge species in transmission of AIV between wild aquatic birds and poultry farms of between poultry farms.

  • Diagnostic tools

    Avian influenza can be diagnosed by virus isolation in embryonated eggs with confirmation of the virus by AGID or ELISA. Conventional and real time RT-PCR assays (RT-qPCR) can identify avian influenza viruses in clinical samples, and can replace virus isolation. RT-qPCRs can partially replace nucleotide sequencing to distinguish sub- and pathotypes. Rapid antigen detection tests have markaedly diminished sensitivity compared to RT-qPCRs and should be used with caution to identify avian influenza only on a flock level but not in individual birds.

    Serological tests including agar gel immunodiffusion (AGID), hemagglutination, hemagglutination inhibition (HI) and ELISAs are useful. Serology can be valuable for active surveillance, to demonstrate freedom from infection with AIV and to check the efficacy of vaccination campaigns. Gallinaceous poultry will be dead from HPAIV infection before mounting antibodies. AGID tests and generic competitive ELISAs can recognize all avian influenza subtypes in poultry, but HI tests are subtype specific and may miss some infections due to high specificity of this assay which does not necessarily include all strains within one subtype.

    GAPS

    • Integrated and multiplexed rapid molecular tests (both pen-side and high-throughput lab tests) to detect and characterize all influenza viruses timely and cost effectively.
    • Better serological tests to determine the subtype specificity of antibodies (i.e. to identify what subtype an animal has been infected with) and to determine antigenic characteristics of influenza viruses for improved evaluation of cross reaction/protection between viruses/vaccines.
    • Improve virus recovery methods relating to sample sources, quality and virus isolation
    • Integration of diagnostic methodologies with surveillance (real time data exchange)
    • Integration of diagnostics with bio-informatic approaches to assist decision making

  • Vaccines

    H5, H7, H9 vaccines available, no vaccination of wild birds possible. Inactivated whole virus vaccines, recombinant vaccines (fowl pox, HVT and NDV vectored vaccines). There are five types of AI vaccines possible, inactivated, live, subunit, recombinant vectors expressing AI genes, and DNA vaccines. Each of which has both advantages and disadvantages to its use. Although various types of AI vaccines have been tested in experimental conditions, only relatively few have been licensed in industrialized countries. Traditionally, inactivated vaccines have been based on antigens produced from naturally low pathogenic (LP) AI isolates or HPAI that were modified to be LPAI by reverse genetics. Many factors can contribute to the quality and potency of inactivated vaccine including the intrinsic immunogenicity of the viral seed strain, the quantity and quality of viral antigen, the emulsion, the stability and the batch-to-batch consistency. The antigenic relatedness between the vaccine strain and the field virus against which protection is targeted should be as close as possible to ensure a high efficacy of vaccination.

    GAPS

    Availability, delivery mechanisms and efficacious cross-protective vaccines:

    • Vaccines have limited cross-protection against antigenic variants within a subtype, even less protection between subtypes (e.g., multivalent vaccines).
    • Veterinary and human health coordination in vaccine seed strain selection to minimize generation of drift mutants and to maximize vaccine efficacy.
    • A strategy based on DIVA-vaccines is missing.
    • Lack of vaccine delivery mechanisms that could be used in mass application (e.g. via drinking water or spray) and/or hatchery vaccination
    • Evaluation of antigenic consequences of genetic diversity, including epitope mapping
    • Need for public/private partnership to develop emergency vaccines
    • Perform vaccine efficacy studies in conditions similar to field situation to understand the different factors in the field that make vaccination less efficient than under controlled experimental conditions.
    • Evaluate the interference of maternally-derived antibodies on vaccine efficacy
    • Develop vaccines with broad efficacy against preferably several subtypes
    • Duck vaccination is important in countries with endemic infection
    • Country-specific autogenous vaccines may be considered

  • Therapeutics

    None

  • Biosecurity measures effective as a preventive measure

    Poultry producers should maintain a high level of biosecurity on farms and hatcheries.

    GAPS
    • What is a sufficient level of biosecurity according to different poultry production sectors.
    • Needs to be broken down into specific measures.
    • Organic and free range poultry production pose special risks related to an increased interface to aquatic wild bird and bridge bird populations. How can such risks be minimized/compensated?

  • Border/trade/movement control sufficient for control

    Control on the movement of birds and products from infected regions.

  • Prevention tools

    Biosecurity and vaccines

  • Surveillance

    AI viruses evolve rapidly along lines defined by specific selection pressures such as population immunity (also vaccine-induced immunity) or host specific barriers of replication (transspecies transmission events). A sustainable monitoring system of the antigenic characteristics and tropisms of circulating AI viruses in enzootically infected poultry populations by testing new viruses isolates must be installed. Surveillance in population free of AIV infections should first aim at early detection and eradication of incursions. Veterinary authorities may use information provided through surveillance to guide decision-making when establishing vaccine banks for use in avian species (Beato et al., 2009). Active virological surveillance is required where viruses are endemic or incursions of viruses expected that do not induce clinically overt symptoms in poultry hosts. Otherwise, syndromic (passive) surveillance (in the absence of vaccination) may be sufficient at first line to detect incursions or follow the spread of virus.

    GAPS

    Monitoring and reporting of virus evolution in different species:

    • A permanent system is needed to regularly analyse and report results of sequencing efforts on a single gene or whole virus genome level to monitor virus evolution in avian, swine and equine populations.
    • Targeted surveillance of migratory wild birds resting places which are hotspots for virus transmission to native waterfowl and for genetic reassortment of the virus.
    • Routine testing is required to screen for potentially pandemic viruses and data should be reported timely.
    • Need to characterize viruses from new outbreaks and collect detailed epidemiological, genomic, antigenic and phenotypic information.
    • Strengthen collaboration between public health and veterinary services (One Health approach).

    Methodologies to analyse virus evolution, estimate risks and simulate possible scenarios and to inform decision making:

    • Standardization of definitions, data collection and data storage at global level. Continuation of databases across & beyond projects
    • Need for (systematic and sustained) application of molecular epidemiology by combining time, geographic location and phylogenetic data, linked with diagnostics and bioinformatics.
    • Integration and validation of risk assessment frameworks.
    • Further development of modelling approaches to simulate possible scenarios to inform policy decisions.
    • Fill most important data gaps that impair decision making, e.g. link between experimental and surveillance data with specific reference to viral and host determinants adaptation.

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

    Eradication of the disease in poultry relies on early detection and rapid response to any outbreak. Removal of infected or in contact birds from the production chains either by culling (HPAIV) or safe slaughtering (notifiable LPAIV) is essential to limit spread. Countries where national veterinary services do not comply with OIE standards on quality are often unable to detect and respond to outbreaks rapidly enough to prevent entrenchment of virus. In these situations, systematic vaccination should be used as an intermediate control measure. Live poultry marketing (LPM) systems have proven to be highly vulnerable to the entrenchment and continued spread of AIV; in particular they present a wide interface area of poultry-to-human contacts. Closure, at least temporarily, of LPMs have shown to be highly effective in curtailing human cases of LPAIV H7N9 in China.

    GAPS

    Measuring/evaluating efficiency of:

    • veterinary services
    • ombination of structure and nature of the poultry sector (including markets), quality of vet services and overall commitment to eradication (as distinct from control)
    • Replacement systems for live poultry marketing.

  • Costs of above measures

    High, for rigorous measures such as stand-still and culling as well as for (long term) relaxed measures including vaccination.

    GAPS

    • Reliable compensations to farmers as an incentive of reporting disease.
    • Sustainability of measures of longer periods.

  • Disease information from the WOAH

  • Disease notifiable to the WOAH

    Yes

    Direct links to the WOAH.

  • Socio-economic impact

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

    Unknown.

    GAP

    • Only if virus becomes human pandemic strain or more readily transmissible from birds to humans will this be significant.

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

    Potentially high with the need for vaccination and antiviral treatment if the incidence in humans increases. But not at present.

    GAPS

    Potentially huge if severe pandemic strain emerges but likelihood appears low based on experiences from past 15 years.

  • Direct impact (a) on production

    Losses to the poultry and allied industries in an outbreak can be severe. A major outbreak could reduce the supply of meat and eggs produced within the country. Highly pathogenic avian influenza (HPAI) virus spreads rapidly, may cause serious disease and result in high mortality rates (up to 100% within 48 hours) in gallinaceous poultry.

    GAPS
    • Market shocks due to consumer fears.
    • More research needed on economic direct and indirect socio-economic impacts, including the impacts of the control measures (e.g. culling programmes affecting availability and price of eggs).

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

    High costs of eradication, vaccination, biosecurity, and surveillance programmes.

  • Indirect impact

    High and severe. Trade implications. Impact on backyard poultry and protein supply of developing countries. Negative impact for tourism in a severely affected region although so far very little evidence that H5N1 HPAI has had any effect on tourism – but would if became pandemic – unlike SARS which did. High and severe. Trade implications. Impact on backyard poultry and protein supply of developing countries. Negative impact for tourism in a severely affected region although so far very little evidence that H5N1 HPAI has had any effect on tourism – but would if became pandemic – unlike SARS which did.

    GAPS
    • Unknown impacts on egg-grown human seasonal influenza vaccine production in case of severe outbreaks in regions where layer herds for SPF egg production are kept.
    • More research needed on economic direct and indirect socio-economic impacts, including the impacts of the control measures (e.g. culling programmes affecting availability and price of eggs).

  • Trade implications

  • Impact on international trade/exports from the EU

    If an outbreak of HPAI occurred, exports of live birds, eggs and poultry products would initially be prohibited from the affected Member state and possibly from others in the EU into third countries. Concepts of regionalization and compartmentalization may diminish impacts. Details of standards are contained in the OIE Terrestrial Animal Health Code 2009 chapter 10.4 Avian influenza

    GAP

    • Need for pre-approved compartments and integrated production chains with on-going monitoring.

  • Impact on EU intra-community trade

    See above.

  • Impact on national trade

    Depending on size, intensity and region of outbreak. Significant to severe, if areas of high density poultry population are concerned or hatcheries, nucleus breeding herds etc. are affected by restriction measures. Low to negligible if infection is detected and eradicated on the index holding in areas with low poultry population densities.

  • Links to climate

    Seasonal cycle linked to climate

    Yes for both LPAIV and HPAIV. The climate affects the presence of migratory birds. E.g. Higher incidence in Autumn and Winter. However, recent epidemiology is changing with year round outbreaks.

    GAP

    • Year round surveillance and biosecurity measures need to be implemented.

  • Distribution of disease or vector linked to climate

    Suspected for HPAIV in wild birds avoiding regions with low temperatures (0°C isotherm)

  • Outbreaks linked to extreme weather

    Suspected for HPAIV in wild birds (extreme cold spells influencing migration of wild birds to other regions)

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

    Not known

    GAP

    • Climate change has an effect on the number of migrating birds as well as on the migration routes. The effects on AI epidemiology should be studied.

Risk

  • Vaccination is an important method for controlling avian influenza but can pose some risks. It would be possible to stimulate accelerated antigenic drift if vaccines are not applied properly and scattered population immunity results. Likewise, without proper marker systems, it will be difficult to differentiate serologically infection-related from vaccination-induced antibody responses. This is turn will have impact on epidemiological investigations. Problems of available vaccines to induce sterile immunity implies risks of silent spread of virus by healthy appearing infected vaccinated poultry. Intensive and sustained monitoring of vaccinated herds by genetic DIVA is required.

    GAPS: Need to weigh up advantages of vaccination against these disadvantages in endemically infected countries in places where it will not be possible to eliminate virus in the foreseeable future due to the structure of the sector, quality of vet services and the limited commitment at all levels to measures required for disease elimination.

Main critical gaps

    • Identify virus and host determinants of virus replication to understand host range restriction and to identify mechanisms by which viruses adapt to new host species.
    • Integrated and multiplexed rapid molecular tests.
    • Improve serological tests.
    • Improve virus recovery methods.
    • Develop integrated risk assessment tools.
    • Interface studies of different host species.
    • Analyse risk of introduction (risk factors and mechanisms/ preventive measures) and early detection.
    • Develop an efficacious emergency vaccination program for animal influenza viruses with pandemic and/or epizootic potential.
    • Validate biosecurity measures to avoid introduction & spread of avian influenza, with particular focus on life bird markets in e.g. Africa and Asia.
    • Research on the development of routine vaccination and route of inoculation: mass vaccination = drinking water or spray.
    • Field studies on these parameters are lacking.

Conclusion

  • On the workshop on Research Gap Analysis in Animal Influenza (Parma, 8-9 January 2015) organized by EFSA and the European Commission’s DG for Agriculture and Rural Development and DG Research and Innovation, ten research priority subjects were identified and described among four main research domains: host-pathogen interaction, diagnosis, surveillance and prevention and control. The identified subjects were: · Identify virus and host determinants of virus replication to understand host range restriction and to identify mechanisms by which viruses adapt to new host species. · Integrated and multiplexed rapid molecular tests. · Improve serological tests. · Improve virus recovery methods. · Develop integrated risk assessment tools. · Interface studies of different host species. · Analyse risk of introduction into EU (risk factors and mechanisms/ preventive measures) and early detection. · Develop an efficacious emergency vaccination program for animal influenza viruses with pandemic and/or epizootic potential. · Validate biosecurity measures to avoid introduction & spread of avian influenza. · Research on the development of routine vaccination. Route of inoculation: mass vaccination = drinking water or spray. Field studies on these parameters are lacking. In the same vein the FAO/WOAH Global Framework for the Progressive Control of Transboundary Animal Diseases (GF-TADs) launched the global strategy for the prevention and control of HPAI (2024-2033) in March 2025. The goal of sustainably reducing the impacts of HPAI on poultry, improving the resilience of poultry, agri-food systems, safeguard ecosystem, and protect animal and human health was cited. The main objectives of the strategy are to prevent, to protect and to transform responses to AI through leveraging a network of global efforts including DISCONTOOLS. Regular updating of DISCONTOOLS recommendations in line with global best practices even as the virus keeps changing ensures our efforts to control AI are fit for purpose and effective.

Sources of information

  • Expert group composition

    Clement Meseko - National Veterinary Research Institute (NVRI), Nigeria – [Leader]

    Isabella Monne - Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Italy

    Anja Globig - Friedrich-Loeffler-Institut (FLI), Germany

    Marie Culhane - University of Minnesota College of Veterinary Medicine, USA

    Frank Wong - Australian Centre for Disease Preparedness (ACDP), CSIRO, Australia

    Yohannes Berhane - National Center for Foreign Animal Diseases, Canada

    Abubakar Woziri - Ahmadu Bello University, Nigeria

    Gonzales Rojas, Jose - Wageningen Bioveterinary Research, the Netherlands

  • Reviewed by

    Project Management Board.

  • Date of submission by expert group

    27th March 2025