The high pathogenic avian influenza (HPAI) A/goose/Guangdong/1/1996 H5N1 (Gs/Gd) lineage was identified for the first time in poultry in China. The HA gene diversified into 10 clades (0-9) that further subdivided into subclades. Later on in 2005, the virus specially strains from clade 2.2 spread outside Asia reaching to Europe, Middle east and Africa. The HPAI H5N1 clade 2.2 virus caused sever clinical disease with huge economic losses and became endemic in some African and Asian countries that used the vaccination to control the disease.

Since 2014, subclade 2.3.4.4, which originated in China in 2008, has been responsible for all the Gs/Gd lineage epidemic waves reported across Asia, Europe, Africa, and North America. According to the World Health Organization (WHO), this clade has evolved into eight subclades (a–h), with 2.3.4.4b being responsible for the largest HPAI epidemic waves recorded in 2016–2017 (mainly H5N8), 2020–2021, 2021–2022, and 2022–2023 (mainly H5N1). These viruses (clade 2.3.4.4b) becoming a serious global threat for poultry, as well as several mammals and representing a zoonotic risk for human health with 962 HPAI A(H5Nx) zoonotic infections reported up to 14 July 2023.

The H5Nx HPAIVs clade 2.3.4.4b have strong ability for reassortment with different low pathogenic AIVs circulating in the wild birds from Asia, Europe and Americas generating up to 16 genotype (1-16), producing highly adapted strains to wide range of wild bird species. This adaptation obvious in the long-distance transmission between different continents as these viruses replicates very well with high titers without causing mortalities to migratory birds. This made the migratory wild birds the main reservoir for these viruses with recurrent introductions recorded in many countries all over the world.

The H5N8 and H5N1 viruses have multi-basic amino acids at the HA cleavage site as HPAI viruses with high pathogenicity indexes in chickens, however, the pathogenicity differs according to species, breed, age, and vaccination. Chickens and turkeys were the most susceptible with high mortality up to 100% if there is no vaccination. There is no significant difference in pathogenicity between chicken and turkey different breeds and ages, however the virus showed higher pathogenicity in young ages if there is no passive (MDA) or active (vaccination) immunity. Broiler flocks that not vaccinated showed sudden high mortality that reach to 100% in few days (usually around 25 days-old as if infection happened before 20 days-old, MDA will interfere the virus and the clinical disease will differ). Layers and breeders showed high mortalities that can reach up to 90% if there is no vaccination with cyanosis in comb and wattles, shank edema and hemorrhages, stop egg production, nervous and respiratory signs plus necrotic and/or hemorrhagic lesions in pancreas, also lung, viscera and trachea. Vaccinated flock will show different levels of protection in clinical signs, mortalities, and virus shedding according to the vaccine application and H5 strain included in addition to flock management and presence of other infections.

On the other hand, different pathogenicity observed in ducks breeds with Muscovy most susceptible then Mallard then Pekin ducks. Moreover, young ages of ducks and geese showed severe clinical signs (nervous) with high mortalities (up to 100% specially in gosling and Muscovy duckling but Mallard and Pekin duckling ranged from 20-70%), while adult laying duck and geese were more resistant with milder signs. Mortalities in adult ducks differ between breeds and virus strain (generally low mortalities) but adult geese were 100% resistant with no mortalities. These observations made the adult waterfowl possible reservoir for these viruses inside the country that can easily disseminating the virus to susceptible poultry farms also to contact mammals and human.

The prevention and control of the disease depend on movement control, vaccination and biosecurity measures specially to prevent contact of free flying wild birds with poultry farms plus the backyard duck and geese flocks should be away from susceptible poultry farms. Due to the endemic situation and the frequent introduction of the HPAI H5Nx virus clade 2.3.4.4b each autumn/winter season almost every year, applying vaccination specially with killed vaccines is highly recommended. Good vaccination depends on using matching H5 strain (clade 2.3.4.4b), high antigen mass, and proper application. Single vaccination with killed vaccines in broiler can be sufficient while multiple vaccinations (up to 5 vaccinations) in layer and breeder flocks is recommended to provide protective HI titers. Vaccination with vector HVT-H5 vaccines then multiple vaccinations with killed vaccines is also used in layers and breeders.