21-ICRAD Virulent Non-Notifiable Avian Influenza; Determinants of virulence of emerging viruses

Europe is one of the world's largest poultry meat and egg producers and exporter of poultry products. Disease outbreaks are a major threat for the poultry industry. Avian Influenza (AI) is listed as a top challenge and with that, is a major concern of the European and worldwide poultry industry. In poultry, the severity of AI virus (AIV) strains is classified into Highly Pathogenic (HPAI) or Low Pathogenic (LPAI). HPAI strains cause severe infections and high levels of mortality. HPAI and LPAI of the H5 and H7 types are notifiable diseases, i.e. diseases that are required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. European Member states conduct surveillance programmes and outbreaks involving AI H5 and H7 subtypes are notifiable to the OIE. However, not only LPAI H5 and H7 and HPAI subtypes form a threat for the poultry industry. Several of the non H5/H7 subtypes such as H3 and H9, can be very virulent and infections with these strains can also cause severe production losses. Besides the economic consequences, these virulent non-notifiable LPAI (nn-LPAI) subtypes have a major impact on animal welfare by causing severe clinical symptoms, high mortality rates and - in case of controlling the outbreak - culling of diseased and/or healthy flocks. AI is a zoonotic disease and past influenza pandemics were caused by viruses that were at least partly derived from AI viruses. Therefore, impacts on public health may be great if nn-LPAI with high zoonotic potential are not controlled adequately.

The FluNuance consortium aims to develop a diagnostic tool or identification system for virulent nn-LPAI strains. To achieve this we will first have to understand why these normally low pathogenic viruses become more pathogenic and how they interact with their hosts, chickens and representatives of wildlife: mallard, geese and pigeon. This knowledge will allow us to better assess the potential risks that viruses from the animal reservoir imposes for the poultry industry and vice versa. As a consequence, poultry production will be threatened less by these viruses, thereby reducing negative impacts on animal welfare and decreasing the numbers of flocks that are culled. In case the emerging nn-LPAI has high zoonotic potential, the risk of a pandemic will be lowered. Thus, this proposal addresses the ever-increasing importance of the poultry industry and aligns with the consumers' demands for 'healthy food from healthy animals'.

Disease outbreaks are a major threat for the European poultry industry. Avian Influenza A virus (AIV) is a global problem, causing widespread harm to animal and public health, animal welfare and food production. In poultry, pathogenicity of AIV strains is binary classified into Highly Pathogenic (HPAI) and Low Pathogenic (LPAI), using an intravenous pathogenicity index (IVPI) test in 6-week-old chickens and/or the presence of multiple basic amino acids at the cleavage site of the virus hemagglutinin (HA). Many non-notifiable (nn-LPAI; i.e. non H5/H7 subtype) AIV strains usually cause mild or moderate infections, but with highly variable mortality. High virulence nn-LPAIVs are not predicted by IVPI, as shown by recent outbreaks in Belgium, where an H3N1 strain formally classified as LPAI (IVPI = 0.13) nevertheless caused >50% mortality and a 100% drop in egg production.

The FluNuance consortium aims to understand the determinants of increased virulence of LPAI in chickens and representatives of wildlife: mallard,
geese and pigeon, and to extrapolate this to host cell tropism in order to better assess the potential risks that viruses from the animal reservoir imposes for the poultry industry and vice versa. Since these viruses may have a significant impact on animal health and welfare, we will determine the biomarkers and develop tools to predict high virulence of non-H5/H7 viruses.