Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020.

Analyses of HPAI H5 viruses from poultry outbreaks across a wide Eurasian region since July 2020 including the Russian Federation, Republics of Iraq and Kazakhstan, and recent detections in migratory waterfowl in the Netherlands, revealed undetected maintenance of H5N8, likely in galliform poultry since 2017/18 and both H5N5 and H5N1. All viruses belong to A/H5 clade 2.3.4.4b with closely related HA genes. Heterogeneity in Eurasian H5Nx HPAI emerging variants threatens poultry production, food security and veterinary public health.

Regional Transmission and Reassortment of 2.3.4.4b Highly Pathogenic Avian Influenza (HPAI) Viruses in Bulgarian Poultry 2017/18.

Between 2017 and 2018, several farms across Bulgaria reported outbreaks of H5 highly-pathogenic avian influenza (HPAI) viruses. In this study we used genomic and traditional epidemiological analyses to trace the origin and subsequent spread of these outbreaks within Bulgaria. Both methods indicate two separate incursions, one restricted to the northeastern region of Dobrich, and another largely restricted to Central and Eastern Bulgaria including places such as Plovdiv, Sliven and Stara Zagora, as well as one virus from the Western region of Vidin. Both outbreaks likely originate from different European 2.3.4.4b virus ancestors circulating in 2017. The viruses were likely introduced by wild birds or poultry trade links in 2017 and have continued to circulate, but due to lack of contemporaneous sampling and sequences from wild bird viruses in Bulgaria, the precise route and timing of introduction cannot be determined. Analysis of whole genomes indicates a complete lack of reassortment in all segments but the matrix protein gene (MP), which presents as multiple smaller clusters associated with different European 2.3.4.4b viruses. Ancestral reconstruction of host states of the hemagglutinin (HA) gene of viruses involved in the outbreaks suggests that transmission is driven by domestic ducks into galliform poultry. Thus, according to present evidence, we suggest the surveillance of domestic ducks as they are an epidemiologically relevant species for subclinical infection. Monitoring the spread due to movement between farms within regions and links to poultry production systems in European countries can help to predict and prevent future outbreaks. The 2.3.4.4b lineage which caused the largest recorded poultry epidemic in Europe continues to circulate, and the risk of further transmission by wild birds during migration remains.

Quantifying the spatial risk of Avian Influenza introduction into British poultry by wild birds.

The transmission of pathogens across the interface between wildlife and livestock presents a challenge to the development of effective surveillance and control measures. Wild birds, especially waterbirds such as the Anseriformes and Charadriiformes are considered to be the natural hosts of Avian Influenza (AI), and are presumed to pose one of the most likely vectors for incursion of AI into European poultry flocks. We have developed a generic quantitative risk map, derived from the classical epidemiological risk equation, to describe the relative, spatial risk of disease incursion into poultry flocks via wild birds. We then assessed the risk for AI incursion into British flocks. The risk map suggests that the majority of AI incursion risk is highly clustered within certain areas of Britain, including in the east, the south west and the coastal north-west of England. The clustering of high risk areas concentrates total risk in a relatively small land area; the top 33% of cells contribute over 80% of total incursion risk. This suggests that targeted risk-based sampling in a relatively small geographical area could be a much more effective and cost-efficient approach than representative sampling. The generic nature of the risk map method, allows rapid updating and application to other diseases transmissible between wild birds and poultry.

Assessing effects from four years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle, 2013-2017.

The objective was to measure the association between badger culling and bovine tuberculosis (TB) incidents in cattle herds in three areas of England between 2013-2017 (Gloucestershire and Somerset) and 2015-2017 (Dorset). Farming industry-selected licensed culling areas were matched to comparison areas. A TB incident was detection of new Mycobacterium bovis infection (post-mortem confirmed) in at least one animal in a herd. Intervention and comparison area incidence rates were compared in central zones where culling was conducted and surrounding buffer zones, through multivariable Poisson regression analyses. Central zone incidence rates in Gloucestershire (Incidence rate ratio (IRR) 0.34 (95% CI 0.29 to 0.39, p < 0.001) and Somerset (IRR 0.63 (95% CI 0.58 to 0.69, p < 0.001) were lower and no different in Dorset (IRR 1.10, 95% CI 0.96 to 1.27, p = 0.168) than comparison central zone rates. The buffer zone incidence rate was lower for Gloucestershire (IRR 0.64, 95% CI 0.58 to 0.70, p < 0.001), no different for Somerset (IRR 0.97, 95% CI 0.80 to 1.16, p = 0.767) and lower for Dorset (IRR 0.45, 95% CI 0.37 to 0.54, p < 0.001) than comparison buffer zone rates. Industry-led culling was associated with reductions in cattle TB incidence rates after four years but there were variations in effects between areas.

Annual Report on surveillance for avian influenza in poultry and wild birds in Member States of the European Union in 2018.

Avian influenza (AI) is a viral infectious disease that affects all species of domestic and wild birds. The viruses causing this disease can be of high (HPAI) or low (LPAI) pathogenicity and represent a continuous threat to poultry in Europe. Council Directive 2005/94/EC requests EU Member States (MSs) to carry out surveillance in poultry and wild birds and notify the results to the responsible authority. Therefore, MSs and Switzerland have implemented surveillance programmes to yearly monitor incursions of AI viruses in poultry and wild birds. EFSA received a mandate from the European Commission, to collate, validate, analyse and summarise in an annual report the data resulting from the avian influenza surveillance programmes. This is the first report produced under this mandate summarising the results of the surveillance activities carried out in poultry and wild birds in 2018. Overall 18,596 poultry establishments were sampled, of which 43 were seropositive for H5 AI and two for H7 AI. Seropositive establishments were found in 11 MSs, with the highest percentage of seropositive establishments being found in waterfowl gamebird, and geese and duck breeding establishments. A total of 9,145 dead/moribund wild birds were sampled, with 163 birds testing positive to HPAI virus H5N6. The infected birds were reported by eight MSs and were mostly found between January and April 2018. In this report, the wild bird species affected with HPAI are described and the strategy of targeted sampling is assessed. The crude odds ratio of HPAI detection as a function of the target species (species belonging to the list of target species versus species not belonging to the target list) is presented. The surveillance findings for poultry and wild birds for 2018 are also discussed in relation to findings from previous years and current knowledge on the epidemiology of AI in Europe.

Comparison of 2016-17 and Previous Epizootics of Highly Pathogenic Avian Influenza H5 Guangdong Lineage in Europe.

We analyzed the highly pathogenic avian influenza (HPAI) H5 epizootic of 2016-17 in Europe by epidemiologic and genetic characteristics and compared it with 2 previous epizootics caused by the same H5 Guangdong lineage. The 2016-17 epizootic was the largest in Europe by number of countries and farms affected and greatest diversity of wild birds infected. We observed significant differences among the 3 epizootics regarding region affected, epidemic curve, seasonality, and outbreak duration, making it difficult to predict future HPAI epizootics. However, we know that in 2005-06 and 2016-17 the initial peak of wild bird detections preceded the peak of poultry outbreaks within Europe. Phylogenetic analysis of 2016-17 viruses indicates 2 main pathways into Europe. Our findings highlight the need for global surveillance of viral changes to inform disease preparedness, detection, and control.

Reporting Avian Influenza surveillance.

Avian influenza viruses infect domestic poultry and wild birds as well as humans. In poultry, depending on whether these viruses are of high pathogenicity (HPAI) or low pathogenicity (LPAI), the infection can cause different clinical signs, with HPAI causing high mortality in poultry flocks. In order to ensure early detection of avian influenza viruses, surveillance in poultry and wild birds is considered essential. In 2010, the European Commission provided some guidelines to Member States (MSs) on how this surveillance should be carried out, both in poultry and wild birds. EFSA received a mandate from the Commission to collate, validate, analyse, and summarise in an annual report the data resulting from the ongoing avian influenza surveillance programmes established in the different MSs. To deliver on this mandate, EFSA, in collaboration with the Standing Working Group on AI, initiated its activities with the drafting of a scientific report where the future vision of this collection framework was presented. Initial and later drafts of this report were shared with MS representatives in order to get feedback on the practicalities concerning the collection and submission of avian influenza surveillance data to EFSA. In the present report, the data that MSs are legally requested to submit to EFSA ('mandatory') and also the data that would be important to collect in order to optimise the outputs ('desirable') are described. A number of actions that would lead to the optimal data collection are also presented and the added value to MSs is discussed. A step-by-step implementation of the outlined actions is anticipated, with a description of the initial collection framework for 2019 being included in this report.

Avian influenza overview August - November 2018.

Between 16 August and 15 November 2018, 14 highly pathogenic avian influenza (HPAI) A(H5N8) outbreaks in poultry establishments in Bulgaria and seven HPAI A(H5N6) outbreaks, one in captive birds in Germany and six in wild birds in Denmark and the Netherlands were reported in the European Union (EU). No human infection due to HPAI A(H5N8) and A(H5N6) viruses have been reported in Europe so far. Seroconversion of people exposed during outbreaks in Russia has been reported in one study. Although the risk of zoonotic transmission to the general public in Europe is considered to be very low, appropriate personal protection measures of people exposed will reduce any potential risk. Genetic clustering of the viruses isolated from poultry in Bulgaria suggests three separate introductions in 2016 and a continuing circulation and transmission of these viruses within domestic ducks. Recent data from Bulgaria provides further indication that the sensitivity of passive surveillance of HPAI A(H5N8) in domestic ducks may be significantly compromised. Increased vigilance is needed especially during the periods of cold spells in winter when aggregations of wild birds and their movements towards areas with more favourable weather conditions may be encouraged. Two HPAI outbreaks in poultry were reported during this period from western Russia. Low numbers of HPAI outbreaks were observed in Africa and Asia, no HPAI cases were detected in wild birds in the time period relevant for this report. Although a few HPAI outbreaks were reported in Africa and Asia during the reporting period, the probability of HPAI virus introductions from non-EU countries via wild birds particularly via the north-eastern route from Russia is increasing, as the fall migration of wild birds from breeding and moulting sites to the wintering sites continues. Furthermore, the lower temperatures and ultraviolet radiation in winter can facilitate the environmental survival of any potential AI viruses introduced to Europe.

Avian influenza overview November 2017 - February 2018.

Between 16 November 2017 and 15 February 2018, one highly pathogenic avian influenza (HPAI) A(H5N6) and five HPAI A(H5N8) outbreaks in poultry holdings, two HPAI A(H5N6) outbreaks in captive birds and 22 HPAI A(H5N6) wild bird events were reported within Europe. There is a lower incursion of HPAI A(H5N6) in poultry compared to HPAI A(H5N8). There is no evidence to date that HPAI A(H5N6) viruses circulating in Europe are associated with clades infecting humans. Clinical signs in ducks infected with HPAI A(H5N8) seemed to be decreasing, based on reports from Bulgaria. However, HPAI A(H5N8) is still present in Europe and is widespread in neighbouring areas. The majority of mortality events of wild birds from HPAIV A(H5) in this three-month period involved single birds. This indicates that the investigation of events involving single dead birds of target species is important for comprehensive passive surveillance for HPAI A(H5). Moreover, 20 low pathogenic avian influenza (LPAI) outbreaks were reported in three Member States. The risk of zoonotic transmission to the general public in Europe is considered to be very low. The first human case due to avian influenza A(H7N4) was notified in China underlining the threat that newly emerging avian influenza viruses pose for transmission to humans. Close monitoring is required of the situation in Africa and the Middle East with regards to HPAI A(H5N1) and A(H5N8). Uncontrolled spread of virus and subsequent further genetic evolution in regions geographically connected to Europe may increase uncertainty and risk for further dissemination of virus. The risk of HPAI introduction from Third countries via migratory wild birds to Europe is still considered much lower for wild birds crossing the southern borders compared to birds crossing the north-eastern borders, whereas the introduction via trade is still very to extremely unlikely.

Avian influenza overview February - May 2018.

Between 16 February and 15 May 2018, three highly pathogenic avian influenza (HPAI) A(H5N6) and 11 HPAI A(H5N8) outbreaks in poultry holdings, one HPAI A(H5N6) and one HPAI A(H5N8) outbreak in captive birds, and 55 HPAI A(H5N6) wild bird events were reported in Europe. There is no evidence to date that HPAI A(H5N6) viruses circulating in Europe are associated with clades infecting humans. Fewer HPAI wild bird cases have been detected than during the same period of previous year. Most of mortality events among wild birds involved single birds and species listed in the revised list of target species for passive surveillance. Raptor species constitute 74% of the HPAI-infected wild birds found dead. Those raptor species probably became infected by hunting or scavenging HPAI virus-positive birds, and so raptor cases may predominate later in the course of an HPAI epidemic. Despite the important HPAI virus incursion via wild birds there have been few associated HPAI A(H5N6) outbreaks in poultry. Fifteen low pathogenic avian influenza (LPAI) outbreaks were reported in three Member States. The risk of zoonotic transmission to the general public in Europe is considered to be very low. The situation in Africa and the Middle East should be closely monitored with regards to HPAI A(H5N1) and A(H5N8). Uncontrolled spread of the virus and subsequent further genetic evolution in regions geographically connected to Europe may increase uncertainty and the risk for further dissemination of virus. Long-distance migrating wild birds from southern Africa, e.g. the common tern (Sterna hirundo), may be included in targeted active surveillance schemes at a few priority locations in Europe in order to detect HPAI A(H5)-infected migrating birds early. However, the risk of HPAI introduction from non-EU countries via migratory wild birds to Europe is still considered to be much lower for wild birds crossing the southern borders than for those crossing the north-eastern borders.

Avian influenza.

Previous introductions of highly pathogenic avian influenza virus (HPAIV) to the EU were most likely via migratory wild birds. A mathematical model has been developed which indicated that virus amplification and spread may take place when wild bird populations of sufficient size within EU become infected. Low pathogenic avian influenza virus (LPAIV) may reach similar maximum prevalence levels in wild bird populations to HPAIV but the risk of LPAIV infection of a poultry holding was estimated to be lower than that of HPAIV. Only few non-wild bird pathways were identified having a non-negligible risk of AI introduction. The transmission rate between animals within a flock is assessed to be higher for HPAIV than LPAIV. In very few cases, it could be proven that HPAI outbreaks were caused by intrinsic mutation of LPAIV to HPAIV but current knowledge does not allow a prediction as to if, and when this could occur. In gallinaceous poultry, passive surveillance through notification of suspicious clinical signs/mortality was identified as the most effective method for early detection of HPAI outbreaks. For effective surveillance in anseriform poultry, passive surveillance through notification of suspicious clinical signs/mortality needs to be accompanied by serological surveillance and/or a virological surveillance programme of birds found dead (bucket sampling). Serosurveillance is unfit for early warning of LPAI outbreaks at the individual holding level but could be effective in tracing clusters of LPAIV-infected holdings. In wild birds, passive surveillance is an appropriate method for HPAIV surveillance if the HPAIV infections are associated with mortality whereas active wild bird surveillance has a very low efficiency for detecting HPAIV. Experts estimated and emphasised the effect of implementing specific biosecurity measures on reducing the probability of AIV entering into a poultry holding. Human diligence is pivotal to select, implement and maintain specific, effective biosecurity measures.

Attribution of human VTEC O157 infection from meat products: a quantitative risk assessment approach.

To address the risk posed to human health by the consumption of VTEC O157 within contaminated pork, lamb, and beef products within Great Britain, a quantitative risk assessment model has been developed. This model aims to simulate the prevalence and amount of VTEC O157 in different meat products at consumption within a single model framework by adapting previously developed models. The model is stochastic in nature, enabling both variability (natural variation between animals, carcasses, products) and uncertainty (lack of knowledge) about the input parameters to be modeled. Based on the model assumptions and data, it is concluded that the prevalence of VTEC O157 in meat products (joints and mince) at consumption is low (i.e., <0.04%). Beef products, particularly beef burgers, present the highest estimated risk with an estimated eight out of 100,000 servings on average resulting in human infection with VTEC O157.

Analysis of the antigen combining site: correlations between length and sequence composition of the hypervariable loops and the nature of the antigen.

It has long been suggested that the overall shape of the antigen combining site (ACS) of antibodies is correlated with the nature of the antigen. For example, deep pockets are characteristic of antibodies that bind haptens, grooves indicate peptide binders, while antibodies that bind to proteins have relatively flat combining sites. In 1996, MacCallum, Martin and Thornton used a fractal shape descriptor and showed a strong correlation of the shape of the binding region with the general nature of the antigen.However, the shape of the ACS is determined primarily by the lengths of the six complementarity-determining regions (CDRs). Here, we make a direct correlation between the lengths of the CDRs and the nature of the antigen. In addition, we show significant differences in the residue composition of the CDRs of antibodies that bind to different antigen classes. As well as helping us to understand the process of antigen recognition, autoimmune disease and cross-reactivity, these results are of direct application in the design of antibody phage libraries and modification of affinity.