For the first time in the US, highly pathogenic avian influenza (HPAI) has been identified in domestic livestock including goats and dairy cattle. To understand the threat HPAI poses to domestic livestock species, and to inform producers on actions that can be taken to reduce the risk of infection on-farm, the US-based Swine Health Information Center (SHIC) in collaboration with the American Association of Swine Veterinarians (AASV) recently hosted a webinar on influenza A viruses. The recent detection and confirmation of HPAI in domestic livestock by USDA has raised questions regarding the emerging threat and potential risks for swine herds.

Editor’s note: Webinar content has been edited for length and clarity. To watch the full webinar, please visit https://iastate.app.box.com/s/o6dhclv5irvspcbj5q8p21ujr4a9ei29.

Cases of HPAI H5N1 found in livestock

Influenza A viruses affect many warm-blooded animals, including birds and mammals. Some cases of the influenza A H5N1 strain found in poultry have now been reported in livestock.

Dr. Amy Baker, USDA ARS, discusses the biology of influenza A virus in swine and how that impacts swine and human health. Dr. Baker is a research veterinary medical officer and lead scientist of intervention strategies to control endemic and new and emerging influenza A virus infections in swine at the National Animal Disease Center in the US Department of Agriculture based in Ames, Iowa.

Influenza A virus (IAV) is an orthomyxovirus, which means it has a negative strand RNA genome. The virus is enveloped and should be susceptible to most common disinfectants.

“It is important to know IAV is prone to rapid evolution,” Baker says. “Genetic mutation can lead to evasion of population immunity by a process known as antigenic drift. Secondly, IAV is prone to reassortment, which is evolution that can lead to antigenic shift.”

Antigenic shift can happen when a single host is infected by two different influenza strains. When this happens, those segmented genes can shuffle around and combine in new genotypes that can emerge as a new virus in a different population. This is the process that led to the 2009 H1N1 pandemic from multiple swine lineages of influenza A viruses.

While swine influenza can infect many different hosts, it is important to remember that wild water fowl are the native host and support the most diverse HA and NA subtypes. Mammalian-adapted lineages of influenza A viruses in swine include H1N1, H1N2 and H3N2, which can result in exchange of viruses between pigs and people.

“We are becoming aware that cattle may need to be added as a susceptible host for IAV,” Baker says. “As we can see, in the ecology of influenza A virus, flu never rests and is constantly changing.”

Emerging disease surveillance

As such, it is suggested that pigs can be a “mixing vessel” for influenza A viruses, along with other new animal hosts, including humans. Since 2009, we have seen the continued human seasonal transmission of H1N1 from humans to pigs. The spillovers from humans into pigs have greatly added to the diversity of viruses in swine.

Robust surveillance and disease investigation are the foundation for improving intervention strategies for animal health and human health. According to Baker, experts are studying phylogenetics using analytical tools to look at the evolutionary relationships of gene segments in IAV.

Experts are asking the questions:

• What is this?
• Where did it come from?
• When did it happen?
• Did this sequence come from a virus from a bird, a human or another pig?
• Are there interesting patterns over time?

“I really want to emphasize that the diversity of swine IAV has been shaped by human IAV introductions,” Baker says. “There have been more than 680 swine influenza detections from 39 lineages in 24 countries.”

Surveillance for IAV in swine has benefits for swine and public health. The USDA IAV Surveillance System in swine has been active since 2009 through the National Animal Health Laboratory Network (NAHLN). The virus sequences that arise from the surveillance system are deposited in the public database called GenBank, and the summary can be found in octoFLUshow at flu-crew.org. Phylogenetic analysis is available in quarterly reports at https://www.aphis.usda.gov/livestock-poultry-disease/swine/influenza-a-virus.

Producers who suspect an animal disease should contact their veterinarian. Case-compatible swine accessions submitted through the NAHLN can be reimbursed for the testing on samples. This can include:

• Pigs on the farm exhibiting influenza-like illness (ILI)
• Swine populations epidemiologically linked to a human case of IAV
• Swine exhibiting influenza-like illness (ILI) at commingling event, such as auctions, markets, fairs or other swine exhibition events

The USDA is transitioning to a Ct-based threshold for all influenza A virus RT-PCR positive samples, regardless of ILI status. A typical case of a sample submitted to NAHLN would have a FluA RT-PCR with a Ct value cut-off.

Requests for NAHLN authorization of analysis of atypical cases may be made for:

• Unusual virus detected in swine
• Unusual clinical presentation in swine
• Unusual host infected with an influenza A virus

Human-Pig transmission

Humans and pigs exchange IAV at possible interfaces including live animal markets, agricultural exhibits, petting zoos, pig shows and occupational exposure. Understanding the potential risk of swine IAV is important for pandemic planning. When assessing pandemic risks, several factors are considered including pre-existing immunity in the human population, ability to transmit to humans and availability of vaccines.

When a zoonotic swine-lineage IAV is detected in humans, it is called a “variant” to distinguish it from human seasonal and avian lineages. Non-seasonal detections became reportable to World Health Organization (WHO) under the International Health Regulations in 2007. In response, CDC developed PCR tests implemented in public health labs to differentiate variant IAV from seasonal IAV and created a Zoonotic Virus Team. Approximately 500 variants of H3N2, H1N1 and H1N2 subtypes have been detected in the US since 2010.

The CDC routinely checks cross-reactivity of variants against seasonal vaccine strains and the human population. Data on variants and swine IAV are presented twice per year at the WHO consultation meeting on vaccine composition. USDA surveillance system contributes significantly to Offlu swine influenza reports available at https://www.offlu.org/index.php/offlu-vcm-summary-reports/. Significant participation from collaborators outside the US contributes to global surveillance. Through these efforts, scientists have been able to identify novel swine H1 and H3 clades around the world. Thus, a number of of CVV (Candidate Vaccine Virus) from swine origin IAV have been selected for potential pandemic preparedness.

“To summarize, swine influenza viruses are highly diverse in the US and globally,” Baker says. “Repeated introductions of human seasonal influenza contribute to this diversity. Many global swine populations remain under-surveilled. However, the public health-animal health collaboration is a great success story.”

Because avian influenza viruses occasionally infect pigs and other mammals, the current HPAI H5N1 panzootic is a concern for swine health and human pandemic preparedness. With foresight, the labs and detection systems at the NAHLN and National Veterinary Services Laboratories (NVSL) are capable and competent for detecting all IAV in any host.

“Robust surveillance and disease investigation are the foundation for improving intervention strategies for animal health and public health,” Baker says.