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There are 30 recorded epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) from 1959 to early 2012. The largest of these epizootics, affecting more birds and countries than the other 29 epizootics combined, has been the H5N1 HPAI, which began in Guangdong China in 1996, and has killed or resulted in culling of over 250 million poultry and/or wild birds in 63 countries. Most countries have used stamping-out programs in poultry to eradicate H5N1 HPAI. However, 15 affected countries have utilized vaccination as a part of the control strategy. Greater than 113 billion doses were used from 2002 to 2010. Five countries have utilized nationwide routine vaccination programs, which account for 99% of vaccine used: 1) China (90.9%), 2) Egypt (4.6%), 3) Indonesia (2.3%), 4) Vietnam (1.4%), and 5) Hong Kong Special Administrative Region (<0.01%). Mongolia, Kazakhstan, France, The Netherlands, Cote d'Ivoire, Sudan, North Korea, Israel, Russia, and Pakistan used <1% of the avian influenza (AI) vaccine, and the AI vaccine was targeted to either preventive or emergency vaccination programs. Inactivated AI vaccines have accounted for 95.5% of vaccine used, and live recombinant virus vaccines have accounted for 4.5% of vaccine used. The latter are primarily recombinant Newcastle disease vectored vaccine with H5 influenza gene insert. China, Indonesia, Egypt, and Vietnam implemented vaccination after H5N1 HPAI became enzootic in domestic poultry. Bangladesh and eastern India have enzootic H5N1 HPAI and have not used vaccination in their control programs. Clinical disease and mortality have been prevented in chickens, human cases have been reduced, and rural livelihoods and food security have been maintained by using vaccines during HPAI outbreaks. However, field outbreaks have occurred in vaccinating countries, primarily because of inadequate coverage in the target species, but vaccine failures have occurred following antigenic drift in field viruses within China, Egypt, Indonesia, Hong Kong, and Vietnam. The primary strategy for HPAI and H5/H7 low pathogenicity notifiable avian influenza control will continue to be immediate eradication using a four-component strategy: 1) education, 2) biosecurity, 3) rapid diagnostics and surveillance, and 4) elimination of infected poultry. Under some circumstances, vaccination can be added as an additional tool within a wider control strategy when immediate eradication is not feasible, which will maintain livelihoods and food security, and control clinical disease until a primary strategy can be developed and implemented to achieve eradication.

We challenged chickens, turkeys, ducks, quail, and geese with severe acute respiratory syndrome coronavirus 2 or Middle East respiratory syndrome coronavirus. We observed no disease and detected no virus replication and no serum antibodies. We concluded that poultry are unlikely to serve a role in maintenance of either virus.

In late 2014, a H5N8 highly pathogenic avian influenza (HPAI) virus, clade 2.3.4.4, spread by migratory waterfowl into North America reassorting with low pathogenicity AI viruses to produce a H5N2 HPAI virus. Since domestic waterfowl are common backyard poultry frequently in contact with wild waterfowl, the infectivity, transmissibility, and pathogenicity of the United States H5 HPAI index viruses (H5N8 and H5N2) was investigated in domestic ducks and geese. Ducks infected with the viruses had an increase in body temperature but no or mild clinical signs. Infected geese did not show increase in body temperature and most only had mild clinical signs; however, some geese presented severe neurological signs. Ducks became infected and transmitted the viruses to contacts when inoculated with high virus doses [(10 4 and 10 6 50% embryo infective dose (EID 50 )], but not with a lower dose (10 2 EID 50 ). Geese inoculated with the H5N8 virus became infected regardless of the virus dose given, and transmitted the virus to direct contacts. Only geese inoculated with the higher doses of the H5N2 and their contacts became infected, indicating differences in infectivity between the two viruses and the two waterfowl species. Geese shed higher titers of virus and for a longer period of time than ducks. In conclusion, the H5 HPAI viruses can infect domestic waterfowl and easily transmit to contact birds, with geese being more susceptible to infection and disease than ducks. The disease is mostly asymptomatic, but infected birds shed virus for several days representing a risk to other poultry species.

We surveyed the genetic diversity among avian influenza virus (AIV) in wild birds, comprising 167 complete viral genomes from 14 bird species sampled in four locations across the United States. These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection. Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment. From this, we propose that AIV in wild birds forms transient \"genome constellations,\" continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses.

In January 2016, a combined outbreak of highly pathogenic (HP) avian influenza virus (AIV) and low pathogenicity (LP) AIV occurred in commercial turkeys in the state of Indiana, United States. Genetically, the viruses were highly similar, belonged to the North American wild bird lineage, and had not been previously detected in poultry. In order to understand the pathobiology of the H7N8 LPAIV and HPAIV, infectivity, transmission and pathogenicity studies were conducted in chickens, turkeys, and mallards. Among the three species the lowest mean infectious dose for both the LP and HP phenotype was for turkeys, and also disease from the LPAIV was only observed with turkeys. Furthermore, although the HPAIV was lethal for both chickens and turkeys, clinical signs caused by the HPAIV isolate differed between the two species; neurological signs were only observed in turkeys. Mallards could be infected with and transmit both viruses to contacts, but neither caused clinical disease. Interestingly, with all three species, the mean infectious dose of the HP isolate was at least ten times lower than that of the LP isolate. This study corroborates the high susceptibility of turkeys to AIV as well as a pathobiology that is different from chickens. Further, this study demonstrates that mallards can be asymptomatically infected with HP and LP AIV from gallinaceous poultry and may not just be involved in transmitting AIV to them.

Avian influenza (AI) viruses are a diverse group of viruses that can be divided into 144 subtypes, based on different combinations of the 16 hemagglutinin and nine neuraminidase subtypes, and two pathotypes (low and high pathogenicity [HP]), based on lethality for the major poultry species, the chicken. However, other criteria are important in understanding the complex biology of AI viruses, including host adaptation, transmissibility, infectivity, tissue tropism, and lesion, and disease production. Overall, such pathobiological features vary with host species and virus strain. Experimentally, HPAI viruses typically produce a similar severe, systemic disease with high mortality in chickens and other gallinaceous birds. However, these same viruses usually produce no clinical signs of infection or only mild disease in domestic ducks and wild birds. Over the past decade, the emergent HPAI viruses have shifted to increased virulence for chickens as evident by shorter mean death times and a greater propensity for massive disseminated replication in vascular endothelial cells. Importantly, the Asian H5N1 HPAI viruses have changed from producing inconsistent respiratory infections in 2-wk-old domestic ducks to some strains being highly lethal in ducks with virus in multiple internal organs and brain. However, the high lethality for ducks is inversely related to age, unlike these viruses in gallinaceous poultry, which are highly lethal irrespective of the host age. The most recent Asian H5N1 HPAI viruses have infected some wild birds, producing systemic infections and death. Across all bird species, the ability to produce severe disease and death is associated with high virus replication titers in the host, especially in specific tissues such as brain and heart.

The 2014-2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.

In Bangladesh, influenza A(H5N1) viruses are endemic in poultry. Processing infected chickens can aerosolize viruses, increasing the risk for human infections. We evaluated particulate matter (PM ) mass concentration during slaughtering and defeathering methods used in live bird markets in Bangladesh to identify solutions to reduce aerosol exposure. We slaughtered 675 chickens using cones and barrels with 3 lid types and defeathered 45 chickens using a defeathering machine with 5 lid types. We interviewed 3 slaughterers to understand method preference. For slaughtering, barrels with a solid or star-cut lid reduced PM mass concentrations by 65%-73% compared with uncovered barrels. For defeathering, machines fully covered by a solid lid or lid with a hole and pivot door reduced PM mass concentrations by 50% compared with machines with no lid. Slaughterers preferred barrels covered with solid lids and defeathering machines covered with solid or hinged lids. Those methods might reduce aerosol exposure during poultry processing.

Highly pathogenic avian influenza (HPAI) virus subtype H7N3 has been circulating in poultry in Mexico since 2012 and vaccination has been used to control the disease. In this study, eight Mexican H7N3 HPAI viruses from 2015-2017 were isolated and fully sequenced. No evidence of reassortment was detected with other avian influenza (AI) viruses, but phylogenetic analyses show divergence of all eight gene segments into three genetic clusters by 2015, with 94.94 to 98.78 percent nucleotide homology of the HA genes when compared to the index virus from 2012. The HA protein of viruses from each cluster showed a different number of basic amino acids (n = 5-7) in the cleavage site, and six different patterns at the predicted N-glycosylation sites. Comparison of the sequences of the Mexican lineage H7N3 HPAI viruses and American ancestral wild bird AI viruses to characterize the virus evolutionary dynamics showed that the nucleotide substitution rates in PB2, PB1, PA, HA, NP, and NS genes greatly increased once the virus was introduced into poultry. The global nonsynonymous and synonymous ratios imply strong purifying selection driving the evolution of the virus. Forty-nine positively selected sites out of 171 nonsynonymous mutations were identified in the Mexican H7N3 HPAI viruses, including 7 amino acid changes observed in higher proportion in North American poultry origin AI viruses isolates than in wild bird-origin viruses. Continuous monitoring and molecular characterization of the H7N3 HPAI virus is important for better understanding of the virus evolutionary dynamics and further improving control measures including vaccination.

Clade 2.3.4.4 Eurasian lineage H5Nx highly pathogenic avian influenza virus (HPAIV) has become the globally dominant clade and caused global outbreaks since 2014. The clade 2.3.4.4 viruses have evolved into eight hemagglutinin subgroups (2.3.4.4a-h). In this study, we evaluated the infectivity, pathobiology, and transmissibility of seven clade 2.3.4.4 viruses (two 2.3.4.4a, two 2.3.4.4b, one 2.3.4.4c and two 2.3.4.4e) in chickens. The two clade 2.3.4.4e viruses caused 100% mortality and transmissibility in chickens. However, clade 2.3.4.4a and c viruses showed 80-90% mortality and 67% transmissibility. Clade 2.3.4.4b viruses showed 100% mortality, but no transmission to co-housed chickens was observed based on lack of seroconversion. All the infected chickens died showing systemic infection, irrespective of subgroup. The results highlight that all the clade 2.3.4.4 HPAIVs used in this study caused high mortality in infected chickens, but the transmissibility of the viruses in chickens was variable in contrast to that of previous Eurasian-lineage H5N1 HPAIVs. Changes in the pathogenicity and transmissibility of clade 2.3.4.4 HPAIVs warrant careful monitoring of the viruses to establish effective control strategies.