Influenza A Virus in Swine

Swine IAV is an enveloped, negative-stranded RNA virus with a segmented genome and belongs to the Orthomyxoviridae family. IAV has two main antigenic proteins, named hemagglutinin and neuraminidase. These proteins are responsible for viral attachment to cells, release of virions from infected cells, and determination of the virus subtype. There are three main subtypes responsible for influenza infections in pigs (H1N1, H1N2, and H3N2), with multiple strains within each subtype. Other subtypes have been reported sporadically, and influenza B and C viruses have been isolated from pigs but have not been reported to cause the classic disease. Coinfections of IAV with other viruses such as porcine reproductive and respiratory syndrome virus, and bacteria such as Glaesserella parasuis (Glässer disease), Actinobacillus pleuropneumoniae, and Mycoplasma hyopneumoniae are common. The mixing of carrier or subclinically infected animals and susceptible pigs is an important predisposing factor. The virus is readily inactivated by disinfectants.

In North America, outbreaks of IAV in swine occur during all seasons but are most common in fall or winter, often at the onset of particularly cold weather. In warmer areas of the world, infection may occur at any time. Usually, an outbreak is preceded by one or two individual pig cases; the infection then spreads rapidly within a herd, mainly by aerosolization (limited distance), direct pig-to-pig contact, and fomite transfer. Influenza is endemic and widespread in pigs worldwide, and evidence of IAV infection, antibodies, or circulating virus has been well documented in Europe, North America, South and Central America, and Asia. Seroprevalence and viral titers vary among countries, but in general, IAV is considered ubiquitous in the global pig population. All virus subtypes—H1N1, H1N2 and H3N2—are known to circulate in most countries, and cocirculation of subtypes and strains is common on individual farms. Until the 2009 pandemic, very few countries (eg, Norway) had documented records of influenza seronegativity in pigs.

IAV becomes endemic in herds because of the ongoing recruitment of susceptible hosts. In breeding, a herd's piglets, prior to weaning, have been identified as a reservoir of influenza infection capable of spreading IAV to other farms after weaning. Carrier pigs are usually responsible for the introduction of IAV into previously uninfected herds and countries. In addition, lack of strict all-in/all-out practices and movement of pigs between crates or pens are associated with the spread of new influenza infections. In antibody-positive herds, outbreaks of infection recur as immunity wanes. Up to 40% of herds may contain antibody-positive pigs.

The spectrum of IAV infection ranges from subclinical to acute. In the classic acute form, the virus multiplies in bronchial epithelium within 16 hours of infection and causes focal necrosis of the bronchial epithelium, focal atelectasis, and gross hyperemia of the lungs. Bronchial exudates and widespread atelectasis, grossly appearing as plum-colored lesions affecting individual lobules of apical and intermediate lobes, are seen after 24 hours. The lesions continue to develop until 72 hours after infection, after which the virus becomes more difficult to demonstrate. Losses in reproduction associated with outbreaks appear to be secondary to the high fever response, because IAV very rarely causes systemic infection.

A classic acute outbreak of IAV is characterized by sudden onset and rapid spread through the entire herd, often within 1–3 days. The main signs are:

• depression

• anorexia, fever (up to 108°F [42°C]), prostration

• coughing, dyspnea

• weakness

• nasal and ocular mucous discharge

Mortality is generally 1%–4%. The overt course of the disease is usually 3–7 days in uncomplicated infections, with clinical recovery of the herd almost as sudden as the onset. However, virus may continue to cycle among pigs when clinical signs are suppressed by immune responses because pigs may become reinfected with similar or distinct strains. In many herds the main economic loss is from coinfections or secondary infections resulting in stunting and delay in reaching market weight. Some increase in piglet mortality has been reported, and effects on herd fertility, including abortions in late pregnancy and embryonic resorptions, may follow outbreaks in naive herds.

• Presumptive diagnosis based on clinical signs

• RT-PCR and direct viral isolation

IAV is primarily diagnosed by detecting the influenza virus by RT-PCR, virus isolation, and occasionally by detecting antibodies against IAV in nonvaccinated animals. Virus can be isolated from nasal and oral secretions in the febrile phase, from affected lung tissue in the early acute stage, or from udder wipes collected from sows with infected suckling piglets. Sequencing and characterization of the influenza viral isolates may be needed to select epidemiologically relevant strains that may be needed for evaluating virus-specific antibodies or custom vaccine production. A clinical diagnosis (presumptive diagnosis) can be made by observing the sudden onset of a large number of pigs showing coughing, fever, and nasal secretions. However, subclinical and chronic influenza infections are common, and in those cases, cough and nasal secretions may be sporadic.

A retrospective diagnosis can be made by demonstrating a rise in virus-specific antibody titers in acute and convalescent serum samples using the hemagglutination inhibition test. Both H3 and H1 subtype antigens should be included. This test is also used for herd surveys, and an ELISA against the nucleoprotein (not subtype specific) is also available. To diagnose uncomplicated influenza infection, conditions such as pasteurellosis, pseudorabies, porcine reproductive and respiratory syndrome, and chlamydial and Haemophilus infections must be excluded.

• Supportive care including antipyretics and antimicrobials to treat secondary bacterial infections

• Vaccination and improved management practices are necessary for prevention

There is no effective treatment, although antimicrobials may reduce secondary bacterial infections and antipyretics may provide symptomatic relief. Expectorants also may help relieve signs in severely affected herds. Vaccination and strict import controls are the only specific preventive measures. Sow vaccination either prefarrowing or the entire herd at once (mass vaccination) are the most common vaccination protocols. Sow vaccination attempts to maximize the transfer of maternal immunity to the progeny. Piglet vaccination is possible, reduced efficacy due to maternal antibodies is an issue.

Good management practices, such as strict all-in/all-out procedures; limiting movement of pigs and sows within farrowing rooms and between pens, rooms and barns; and freedom from stress, particularly due to crowding and dust, help reduce transmission and losses.

Commercially available killed vaccines that contain both H1N2 and H3N2 subtypes appear to induce a strong protective immune response. In North America, custom-made (autogenous) vaccines prepared with the farm isolate(s) are common, and in 2017 a live-attenuated influenza vaccine became commercially available. Lastly, seasonal vaccination of personnel interacting with pigs is recommended to limit the bidirectional transmission of IAV between pigs and people.

• Zimmerman JJ, Karriker LA, Ramirez A, et al (eds). Diseases of Swine, 11th Edition. Wiley-Blackwell; 2019.

• Salvesen HA and Whitelaw CBA. Current and prospective control strategies of influenza A virus in swine. Porc Health Manag 2021;7(23). https://doi.org/10.1186/s40813-021-00196-0

• Gracia JCM, Pearce DS, Masic A, Balasch M. Influenza A Virus in Swine: Epidemiology, Challenges and Vaccination Strategies. Front Vet Sci. 2020(9). https://doi.org/10.3389/fvets.2020.00647