Pathobiology and innate immune responses of gallinaceous poultry to clade 2.3.4.4A H5Nx highly pathogenic avian influenza virus infection

In the 2014-2015 Eurasian lineage clade 2.3.4.4A H5 highly pathogenic avian influenza (HPAI) outbreak in the U.S., backyard flocks with minor gallinaceous poultry and large commercial poultry (chickens and turkeys) operations were affected. The pathogenesis of the first H5N8 and reassortant H5N2 clade 2.3.4.4A HPAI U.S. isolates was investigated in six gallinaceous species: chickens, Japanese quail, Bobwhite quail, Pearl guinea fowl, Chukar partridges, and Ring-necked pheasants. Both viruses caused 80-100% mortality in all species, except for H5N2 virus that caused 60% mortality in chickens. The surviving challenged birds remained uninfected based on lack of clinical disease and lack of seroconversion. Among the infected birds, chickens and Japanese quail in early clinical stages (asymptomatic and listless) lacked histopathologic findings. In contrast, birds of all species in later clinical stages (moribund and dead) had histopathologic lesions and systemic virus replication consistent with HPAI virus infection in gallinaceous poultry. These birds had widespread multifocal areas of necrosis, sometimes with heterophilic or lymphoplasmacytic inflammatory infiltrate, and viral antigen in parenchymal cells of most tissues. In general, lesions and antigen distribution were similar regardless of virus and species. However, endotheliotropism was the most striking difference among species, with only Pearl guinea fowl showing widespread replication of both viruses in endothelial cells of most tissues. The expression of IFN-γand IL-10 in Japanese quail, and IL-6 in chickens, were up-regulated in later clinical stages compared to asymptomatic birds

Efficacy of novel recombinant fowlpox vaccine against recent Mexican H7N3 highly pathogenic avian influenza virus

Since 2012, H7N3 highly pathogenic avian influenza (HPAI) has produced negative economic and animal welfare impacts on poultry in central Mexico. In the present study, chickens were vaccinated with two different recombinant fowlpox virus vaccines (rFPV-H7/3002 with 2015 H7 hemagglutinin [HA] gene insert, and rFPV-H7/2155 with 2002 H7 HA gene insert), and were then challenged three weeks later with H7N3 HPAI virus (A/chicken/Jalisco/CPA-37905/2015). The rFPV-H7/3002 vaccine conferred 100% protection against mortality and morbidity, and significantly reduced virus shed titers from the respiratory and gastrointestinal tracts. In contrast, 100% of sham and rFPV-H7/2155 vaccinated birds shed virus at higher titers and died within 4 days. Pre- (15/20) and post- (20/20) challenge serum of birds vaccinated with rFPV-H7/3002 had antibodies detectable by hemagglutination inhibition (HI) assay using challenge virus antigen. However, only a few birds (3/20) in the rFPV-H7/2155 vaccinated group had antibodies that reacted against the challenge strain but all birds had antibodies that reacted against the homologous vaccine antigen (A/turkey/Virginia/SEP-66/2002) (20/20). One possible explanation for differences in vaccines efficacy is the antigenic drift between circulating viruses and vaccines. Molecular analysis demonstrated that the Mexican H7N3 strains have continued to rapidly evolve since 2012. In addition, we identified in silico three potential new N-glycosylation sites on the globular head of the H7 HA of A/chicken/Jalisco/CPA-37905/2015 challenge virus, which were absent in 2012 H7N3 outbreak virus. Our results suggested that mutations in the HA antigenic sites including increased glycosylation sites, accumulated in the new circulating Mexican H7 HPAIV strains, altered the recognition of neutralizing antibodies from the older vaccine strain rFPV-H7/2155. Therefore, the protective efficacy of novel rFPV-H7/3002 against recent outbreak Mexican H7N3 HPAIV confirms the importance of frequent updating of vaccines seed strains for long-term effective control of H7 HPAI virus

Pandemic potential of highly pathogenic avian influenza clade 2.3.4.4 A(H5) viruses

The panzootic caused by A/goose/Guangdong/1/96-lineage highly pathogenic avian influenza (HPAI) A(H5) viruses has occurred in multiple waves since 1996. From 2013 onwards, clade 2.3.4.4 viruses of subtypes A(H5N2), A(H5N6), and A(H5N8) emerged to cause panzootic waves of unprecedented magnitude among avian species accompanied by severe losses to the poultry industry around the world. Clade 2.3.4.4 A(H5) viruses have expanded in distinct geographical and evolutionary pathways likely via long distance migratory bird dispersal onto several continents and by poultry trade among neighboring countries. Coupled with regional circulation, the viruses have evolved further by reassorting with local viruses. As of February 2019, there have been 23 cases of humans infected with clade 2.3.4.4 H5N6 viruses, 16 (70%) of which had fatal outcomes. To date, no HPAI A(H5) virus has caused sustainable human-to-human transmission. However, due to the lack of population immunity in humans and ongoing evolution of the virus, there is a continuing risk that clade 2.3.4.4 A(H5) viruses could cause an influenza pandemic if the ability to transmit efficiently among humans was gained. Therefore, multisectoral collaborations among the animal, environmental, and public health sectors are essential to conduct risk assessments and develop countermeasures to prevent disease and to control spread. In this article, we describe an assessment of the likelihood of clade 2.3.4.4 A(H5) viruses gaining human-to-human transmissibility and impact on human health should such human-to-human transmission occur. This structured analysis assessed properties of the virus, attributes of the human population, and ecology and epidemiology of these viruses in animal hosts

Avian influenza control strategies in the United States of America

Prevention, control and eradication are three different goals or outcomes for dealing with avian influenza (AI) outbreaks in commercial poultry of the USA. These goals are achieved through various strategies developed using components of biosecurity (prevention or reduction in exposure), surveillance and diagnostics, elimination of infected poultry, decreasing host susceptibility to the virus (vaccination or host genetics) and education. However, the success of any developed strategy has depended on industry-government trust, co-operation and interaction. The preferred outcome for HPAI has been stamping out, for which the federal government has regulatory authority to declare an emergency and do immediate eradication of HPAI, and pay indemnities. For H5and H7LPAI, strategies vary from an immediate control plan followed by an intermediate to long-term strategy of eradication. The state governments have regulatory authority over H5 and H7 LPAI, but work cooperatively with USDA in joint programmes. Stamping out has been occasionally used as has controlled marketing, but inconsistently, indemnities have been funded by the state governments and the poultry industries, and less frequently by USDA. Vaccines have been occasionally used but require USDA license of the vaccine and approval from both state and federal government before use in the field. Non-H5 and -H7 LPAI generally follow a preventive programme, such as H1N1 swine-influenza vaccination for turkey breeders. In other situations, control and eradication strategies are followed but regulatory authority is lacking for USDA. Most programmes for LPAI are voluntary and industry-driven

The development of avian influenza vaccines for emergency use

Costly outbreaks of mildly and highly pathogenic avian influenza (AI) have occurred in the commercial poultry industry in Europe and the United States in the past two years. The current approach is to control the disease by depopulation of infected flocks followed by cleaning and disinfection of the premises. The cost of eradication of influenza and the payments to the poultry producer continue to increase. The cost of the AI eradication in the Netherlands and the United States was more than 500 million USD. The use of vaccines to control AI is gaining acceptance by veterinary health agencies as a tool in eradication programmes. The choice of vaccines available includes purified subunit vaccines, genetically modified vaccines and the traditional whole-virus inactivated vaccines. The use of inactivated vaccines has been used successfully in many countries to stop the spread of avian influenza in the poultry industry. The fowlpox-vectored vaccine TROVAC AI H5™ has been used to vaccinate broiler chickens in Mexico for five years. The preparation of a supply of vaccine in advance of a disease outbreak has been used in the human health sector. A vaccine bank was created at Merial for foot-and-mouth disease more than 10 years ago. The idea of developing a vaccine bank for avian influenza is being discussed in the United States and in the European Union. Before a strategic plan for AI vaccines can be implemented, many questions about the AI strains needed, the amount of vaccine, the formulation, the priority of vaccination in the poultry industry and the cost to produce and maintain stored antigens or vaccines need to be addressed

Highly pathogenic avian influenza viruses and generation of novel reassortants, United States, 2014-2015

10.3201/eid2207.160048Emerging Infectious Diseases2271283-128

Transmission dynamics of highly pathogenic avian influenzvirus a(H5Nx) clade 2.3.4.4, North America, 2014–2015

10.3201/eid2410.171891Emerging Infectious Diseases24101840-184