Four types of commercial test kits available: Antibody detection ELISA, PCR, lateral flow devices and antigens test for HI available or in development.
GAP: Many commercial kits, especially those developed in Asia have unknown efficacy.
Same as above. Avian Influenza Antibody test kit is on the Register of diagnostic tests certified by the OIE and validated as fit for purpose.
GAP: Easier to use, field-applicable and specific tests required.
Only a single avian influenza antibody test kit is on the register of diagnostic tests certified by the OIE as fit for purpose (http://www.oie.int/our-scientific-expertise/certification-of-diagnostic-tests/the-register-of-diagnostic-tests/). Scattered validation data of several commercial tests available in different reference laboratories in EU; governmentally directed licensing procedure for AI diagnostic kits in place in Germany.
GAP: Meta-analysis of validation data for test kits. Lack of internationally approved standard reagents to validate diagnostic assays/kits.
Details are contained in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2009 Chapter 2.3.4 on Avian influenza; diagnostic manual on avian influenza as issued by EU decision 2006/437/EC. Lists of updated methods supplied by OFFLU network (www.offlu.net).
GAP: Specific SOPs.
Moderate at best; companies focus on Asian markets
Currently the only approach in Europe that can be applied to differentiate infected from vaccinated birds is the use of a heterologous vaccine (vaccine virus with the same H type as the field strain but a different N type). With such a vaccine, the immune response to the homologous H type ensures protection, while antibodies against the neuraminidase allow differentiation between the field and vaccine strains. The advantage of this method is that a vaccine bank of inactivated oil emulsion heterologous vaccines could be established. However, field applicability and high throughput tools for this method are doubtful.
Genetic DIVA concepts, i.e. testing for the presence of acute virus infections in vaccinated flocks by RT-qPCRs, are much more straight forward and easier to implement as compared to above mentioned serological DIVA.
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.
GAP: Better DIVA tests are required. Validity of DIVA for HPAI not yet assessed under field conditions; validity of other methods of assessing infectious status of flocks such as testing of routine mortalities.
Multi strain vaccines, vaccines inducing broad range protection (“universal influenza vaccine”), modified live virus vaccines for mass application purposes that do not reassort with wildtype viruses.. See specifications made in EFSA and O.I.E. reports.
GAP: Registration of vaccines through the MS is a new concept which has recently been introduced within the revised text of annex I to Directive 2009/09, and is illustrated in EMEA/CVMP/IWP/105506/2007 (GL on data requirements for multi-strain dossiers for inactivated vaccines against avian influenza, blue tongue and foot and mouth disease). The consistency and coherence of all submitted data should be based on sound scientific arguments. To facilitate the acceptance of an MS dossier, a list of outstanding issues should be taken into account, such as: selection of one uniform dose size for the target species; justification of the selected virus strains, and combination and number of strains included in the final product; the use of fixed amounts of active ingredients and a stable and clear formulation ratio (adjuvant/buffer). Vaccines with a shelf life as long as possible should be foreseen. Taking into account that limited numbers of vaccine batches might be produced, situations might be faced which require to assign a (rather arbitrary) extension of shelf life to such batches in order to cope with sudden, increased requests from field, e.g. as expected under emergency situation or to complete vaccination campaigns.
H5, H7, H9 vaccines are available. Vaccination of wild birds is not feasible. There are two types of vaccines commercially available at present. Inactivated vaccines and recombinant vaccines (fowl pox, herpesvirus of turkey (HVT) or Newcastle disease virus (NDV) vectors). Recombinant vaccines for AI viruses 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 vaccine and vaccination schedule.
Yes. H5, H7 vaccines for regulated use after approval of a control plan by the EU commission; it has been rarely used in the past: for poultry mainly in Italy but more scattered throughout Europe for zoo bird vaccination (especially until 2010, thereafter discontinuation in most countries). Regional autologous vaccines not licensed for national or EU-wide use are produced in case of local outbreaks of non-notifiable AIV (e.g. H9N2).
GAP: Reporting duties for outbreaks of non-notifiable AIV if industries consider impact severe enough to promote autologous vaccine production.
In principal, yes. DIVA principle with different “N” types. NP antibodies can be used for differentiation in case of recombinant vaccines expressing only H or H and N of AIV. Studies for DIVA using sentinel birds available but information limited. See 15.6 for limited practical usefulness of serologic DIVA.
GAP: Field studies evaluating the DIVA principle using new recombinant vaccines in practise and larger herds.
Not specifically although strains with different N components can be used as markers.
International organisations recommend that vaccines used for AI control must be of high quality and that they should meet international standards and guidelines.
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 commercial potential for AI vaccines in Europe is considered by vaccine manufactures as very low.
GAP: Incentives for vaccine manufacturers to develop new vaccines.
GAP: Need for rapid approval of new seed strains for production.
In the recent years a new approach being developed for the creation of inactivated vaccines for AI is based on the application of reverse genetics techniques (Hofmann, 2002).
Method of application needs to be improved with the long term aim of using spray or drinking water application possible as a single AI vaccine or in combination with Newcastle disease vaccine.
Development of multiple component “H” vaccines may be advantageous.
Ability to build in a vaccination regime for AI into normal husbandry practices along with other preventative vaccinations.
Further development of recombinant vaccines is encouraged, especially using backbones which favour induction of protection in ducks (e.g. duck herpesviruses etc.)
In ovo vaccination needs to be further evaluated.Revisit live virus vaccines (e.g. work by Perez et al) (for instance, temperature sensitive attenuated viruses) and work by Swayne et al. with increased safety so as not to reassert with other AIV in circulation.
None. Antivirals (Tamiflu & Relenza) are effective in poultry but their use is prohibited due to the risk of resistance and hazard thereof for human.
GAP: Not applicable at present stage, however, any therapy should be adapted to the provision in the relevant legislation.
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.
GAPS: Resistant poultry?
There is a requirement for better understanding of the virus and its pathogenic actions. This understanding along with gene sequencing of the virus may lead to the development strain specific antiviral drugs. This would be in the long term objective.
GAP: Cost of antiviral drugs and some limitations in their use under practical conditions.
Tests are needed that are easy to use, 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.
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.
GAP: Continuous need to improve and validate diagnostic tests:
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.
Variable but usually quite long (at least 5 years). Depends on vaccine type, product profile, priorities, registration authorities’ requirements and funding possibilities.
Variable. The proof of concept may be a couple of hundred thousand euros but the full development is several millions euros.
Development of recombinant vaccines, sub unit vaccines and possible DNA vaccines.
GAP: Costs relating to the research and development of some types of vaccines in the face of a potentially limited market.
Not applicable at present.
Not applicable at present.
Not applicable at present.
Not applicable at present.
GAP: Not applicable at present stage, however, any therapy should be adapted to the provision in the relevant legislation.
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.
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.
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.
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: See Section "Variability of the 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.
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 poultryHPAIV: Poultry (in particular domestic waterfowl).
Sources of the virus are mainly faeces and respiratory secretions. Transmission is via contact with infected birds or contaminated fomites (surface water!). AIV is at least moderately contagious but does not spread as explosively as velogenic Newcastle disease virus or infectious bronchitis virus. Oral transmission to mammals possible; other routes of mammalian infection possible (conjunctival transmission).
In case of AIV outbreaks on poultry holdings, the mechanisms of transmission from infected to susceptible farms are not fully understood (aerosol transmission ?), since infection sometimes occurred in farms with high biosecurity measures.
Knowledge regarding virus-host interactions, and on factors that affect virus excretion and spread, to allow more effective infection control, such as:
Knowledge of virus shedding during an HPAI outbreak and consequences of stamping out methods on the release of virus into the environment (aerosolization of virus).
Modes of farm-to-farm transmission in case of outbreaks.
Factors driving persistence and transmissibility of H9N2 infection in farms from endemic regions.
Role of vaccination on kinetics and transmission of LPAI and HPAI in poultry flocks.
Transmission from acutely infected individuals or contaminated fomites to susceptible hosts. Infectious period is short. No evidence as yet for persistent infections/carrier state.
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):
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.
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?
The “low pathogenic” types may spread clinically silent and remain undetected or cause only mild symptoms and, hence, often escape syndromin 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 48 hours in gallinaceous birds in experimental conditions. HPAIV infections in waterfowl can run a much more attenuated course and can be clinically indistinguishable from LPAIV infections.
Following infection virus shedding occurs. Effective infectious period is usually short (1-5 days). Shedding mode (fecal versus oropharyngeal) depends on viral tissue tropism. Vaccination to be fully effective must suppress shedding below the point where it will infect other vaccinated poultry.
GAP: Virus shedding titers and kinetics of shedding in relation to transmission rates & vaccination status.
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.
Low, however, unpredictable zoonotic potential exits. See WHO statistics for HPAIV H5N1 and LPAI H7N9.
GAP: Lack of knowledge of true incidence in humans.
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 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?
Probably low but unknown.
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.
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.
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.
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.
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.
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.
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).
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?
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.
LPAIV: Yes, see Section "Animal infected/carrier/disease"
HPAIV: Likely, see Section "Seasonal cycle (seasonality)"
Suspected for HPAIV in wild birds (0°C isotherm)
Suspected for HPAIV in wild birds (extreme cold spells)
Direct contact with secretions from infected birds, especially faeces, saliva and nasal secretions or contaminated fomites or water is the most common.
Asymptomatically infected aquatic birds may introduce directly or indirectly the virus into flocks.
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.
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 neutrlaizing. 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.
GAP: Understanding of sequence difference of virus-host interactions and factors that impact on immune responses to allow more effective infection control, such as:
Detection of IAV generic and subtype-specific antibodies.
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 2: Enlargement of restriction zones (ban of restocking in large areas)
Phase 3: Implementation of vaccination plan if other measures fail.
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.
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.
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.
GAP: Availability, delivery mechanisms and efficacious cross-protective vaccines:
Poultry producers should maintain a high level of biosecurity on farms and hatcheries.
Control on the movement of birds and products from infected regions.
Biosecurity and vaccines
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.
Monitoring and reporting of virus evolution in different species:
Methodologies to analyse virus evolution, estimate risks and simulate possible scenarios and to inform decision making:
High, for rigorous measures such as stand-still and culling as well as for (long term) relaxed measures including vaccination.
Potentially high with the need for vaccination and antiviral treatment if the incidence in humans increases. But not at present.
Potentially huge if severe pandemic strain emerges but likelihood appears low based on experiences from past 15 years.
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.
GAP: Market shocks due to consumer fears.
High costs of eradication, vaccination, biosecurity, and surveillance programmes.
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.
GAP: 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.
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.
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.
Pandemic scare and increased funds for research.
Food security considerations. Production facilities.Global organisation of commercial poultry companies. Better global surveillance of wild birds and migration patterns. Antigen banks
GAPS: Early detection and timely notification.
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.
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:
GAP: Route of inoculation: mass vaccination = drinking water or spray. Field studies on these parameters are lacking.
Names of expert group participants have been included where permission has been received to do so.
Timm Harder, Friedrich-Loeffler-Institut, Germany [Leader]
Jonas Waldenström, Linnéuniversitetet, Sweden
Michel Bublot, Merial
Project Management Board.
1st of April 2016.
Defra, Animal Diseases, Summary profile for Avian Influenza, Accessed 14 January 2010
Defra, Animal diseases, Disease Factsheet, Avian Influenza, November 2009. Accessed 14 January 2010
Food and Agriculture Organisation, Animal Production and Health Division, Avian Influenza. Accessed 14 January 2010.
OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2009 Chapter 2.3.4 Avian influenza. Accessed 14 January 2010
OIE Terrestrial Animal Health Code 2009 Chapter 10.4 Avian Influenza. Accessed 14 January 2010
OIE-WAHID interface- disease information – Q Fever -list of countries by disease situation: Accessed 11 January 2010
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