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Swine influenza

Swine influenza

G R THOMSON AND B C EASTERDAY
Swine influenza

GENERAL INTRODUCTION: ORTHOMYXOVIRIDAE

Introduction

Swine influenza (SI) is a highly contagious, acute, respiratory disease of pigs caused by type A orthomyxoviruses. It is generally characterized by the sudden onset of a disease manifested by fever, coughing, dyspnoea, nasal discharge, prostration and high morbidity but low mortality rates. The nature of the disease varies according to the strain of the infecting virus, the age and immune status of the animal, and the presence of intercurrent infections. It has a wide distribution in the world.

The place and date of the first recognition of SI is believed to have been on farms in western Illinois, USA, in the summer of 1918 during the time of the worldwide 1918 to 1919 pandemic of human influenza.34 Dr J.S. Koen is credited with being the first person to recognize the disease as being different from any other previously encountered disease of pigs.9 He was impressed with the similarity of the disease in pigs to the influenza in humans.The record indicates that he was the first to apply the name ‘flu’ to the disease in pigs because of the similarity of its clinical signs to the symptoms of influenza in humans, and because of his belief that the two diseases were the same. With the isolation of the influenza virus from pigs in 193033 and from humans in 1933, it was shown that the viruses were related serologically, which lead to speculation that the porcine virus was related to the virus responsible for the disease in humans in 1918 to 1919. It has subsequently been shown by genetic analysis that the 1930 porcine viruses and the 1918 human viruses are closely related.29, 36 It remains unknown whether humans were infected from pigs in 1918 or vice versa.

Aetiology

Influenza viruses belong to the family Orthomyxoviridae and are classified as type A, B or C, based on the antigenic relatedness of the nucleoprotein (NP) and matrix (M) protein. The viral genome consists of eight single-stranded RNA segments. The antigenic nature of the two surface glycoproteins, haemagglutinin (H) and neuraminidase (N) is the basis for dividing the viruses into subtypes. So far, among the type A influenza viruses, there are 15 distinct haemagglutinins and nine neuraminidases. A brief description of the general characteristics of the influenza viruses is provided in Equine influenza.

Swine influenza virus with the antigenic configuration H1N1 has persisted in the USA since it was first identified in the 1930s. Prior to the mid-1970s there were few reports of SI in places other than the USA and no viruses with antigenic characteristics other than the classical swine H1N1 were isolated. H1N1 virus infections in pigs in the UK in 1941,4 Czechoslovakia in 195013 and Germany in 1959 were recorded. 15 Infection of pigs with the H3N2 virus was reported in Taiwan in 1970.19

In recent years viruses with other antigenic configurations have been identified in pigs in various parts of the world. In addition to the classical swine H1N1 virus, there are H1N1 viruses of avian origin, an H4N6 of avian origin, H3N2 viruses, reassortants of H3N2 of both porcine and human origin, and H1N2 virus, a reassortant of classical swine H1N1 and H3N2 viruses.10, 16, 17, 18

Porcine infections with other than type A influenza viruses appear to be rare. Type C influenza virus infections in pigs have been described in Japan and China.11, 40

In southern Africa, infection of pigs with SI viruses has not been recognized although it has been reported in Kenya.31

Epidemiology

Swine influenza is common in countries in North America and Europe (including the UK) and has been identified in at least 25 other countries on all of the continents in the world except Australia.1, 2, 3, 8, 10, 20, 26, 32, 35

Historically, episodes of acute SI in the USA were most commonly reported in late summer and winter, although it was clear, based on viral isolation and serological studies, that the virus was circulating in pigs throughout the year. As more pigs in the temperate climates are being maintained in confinement housing and are therefore not subjected to climatic fluctuations, the disease has become less seasonal in nature.14, 24 In the USA infections occur throughout the year.10, 24, 27

Transmission of the virus is generally by direct contact between infected pigs and susceptible individuals, although infected fomites may also be a source of infection. The first appearance of SI in a population is commonly associated with the movement of animals, such as the introduction of new breeding animals or fattening stock into a herd or the return of stock from agricultural shows to the home farm. The primary method of transmission is direct pig to pig by the nasopharyngeal route. The virus is abundant in nasal secretions during the acute febrile stages of infection. Infection by exposure to small particle aerosols of virus suspensions is readily demonstrated under experimental conditions. Airborne transmission may be responsible for sudden and expanding outbreaks in densely populated areas especially if the populations are immunologically naive.10, 37 Under experimental conditions it was determined that the duration of virus excretion may continue intermittently for as long as four months,5 but the results of another study suggested that the duration of excretion is not longer than four weeks.38 The results obtained in other experimental studies have, however, indicated that virus clearance is very rapid as the virus could not be isolated from the lungs or other respiratory system tissues on or after the seventh day after exposure.6 There are no data available that offer convincing support or rejection of the existence of a true long-term carrier state of influenza viruses in pigs.

Since the northern hemisphere winter of 1979/80, an H1N1 virus that is antigenically and genetically distinct from the classical SI virus but closely related to avian H1N1 viruses has prevailed in the pig populations of Europe.30 The H3N2 viruses have been circulating in pig populations in Europe and Asia for more than 20 years but less frequently in pig populations in North America until the late 1990s. In many areas of Europe, the avian H1N1 and the H3N2 strains have continued to co-circulate continuously and have become endemic.10

It has become clear that there is considerable interspecies transmission of influenza viruses, some by crossing the animal and/or human species barrier in toto and others as a result of reassortment, the progeny resulting from a double infection with antigenically and genetically distinct viruses. The major interspecies events have been between birds and pigs, and humans and pigs, with very little transfer between birds and humans; these all lead to the conclusion that pigs have the ability to function as interspecies intermediates and as ‘mixing vessels’ for evolving new strains of influenza viruses. For greater detail on the role of pigs as intermediate hosts for new influenza viruses and the genetic characterization of evolving influenza viruses, refer to the articles by Scholtissek et al.30 and Karasin et al.16, 17, 18 Given the contemporary history of the changing character of the influenza viruses infecting pigs and the disease(s) that they produce, it is reasonable to expect the appearance of infections caused by such viruses in pigs virtually anywhere in the world, especially when there is close pig to human contact and opportunities for close interaction or intermingling of pig and avian populations.

Pathogenesis

Influenza virus infection in pigs is generally limited to the respiratory tract. In addition to the lungs, virus has been demonstrated in nasal mucosa, tonsils, trachea and tracheobronchial lymph nodes. Virus-specific antigen has been detected in epithelial cells of the respiratory tract within two hours of experimental infection and virions were seen budding from the surface of type II pneumocytes within five hours.3 Virus titres in the lungs of pigs may be greater than 108 EID50 per gram of tissue after intratracheal inoculation.12 More severe disease is likely to result following the inoculation of virus by the intratracheal route as compared to that which occurs after intranasal inoculation with a dose of virus of similar magnitude.22 Immunofluorescence studies have shown the rapidity of replication of the virus and specific tropism for bronchial and bronchiolar epithelial cells within a few hours after infection. Specific viral antigen was also observed in the cells lining the alveoli and alveolar ducts.6, 12, 25 It remains to be seen whether there are differences in the site of replication with the different influenza virus strains. Influenza-specific antibodies have been detected in serum and nasal secretions three and four days respectively after experimental infections using enzyme-linked immunosorbent assay (ELISA) techniques.21

The course and nature of the disease may be influenced by many factors such as immune status, age, infection pressure (magnitude of infecting dose of virus), housing and climatic conditions, and intercurrent infections.

Clinical signs

A sudden onset of an acute respiratory disease with high morbidity rate (approaching 100 per cent) characterizes outbreaks of SI in piggeries. Affected animals usually have high rectal temperatures (up to 42,8 °C), are anorexic, inactive, lie huddled together, and are disinclined to move even when disturbed.28, 37 Severe cases may suffer from apparent muscular weakness and prostration. Respiration may be open-mouthed, laboured, jerky and abdominal, and accompanied by severe paroxysms of coughing, especially when disturbed. During bouts of coughing affected pigs adopt a typical kyphotic posture.3 Conjunctivitis, rhinitis, nasal and ocular discharges that range from slight to moderate and progressing from serous to mucopurulent, and sneezing are frequently observed.

The course of the disease is typically three to seven days, with the speed of recovery being as rapid as the onset, although severely affected individuals may take some weeks to regain their previous physical condition. Mortality rates are usually less than 1 per cent, but intercurrent infections with other infectious agents may change the nature and severity of the disease and the mortality rate. There is increasing evidence that the avian-like H1N1 strains that are circulating in some countries may be more pathogenic than the older classical H1N1 strains.10

While pig producers and veterinarians occasionally report reproductive and farrowing problems, such as abortions, stillbirths, infertility and small or weak litters associated with outbreaks of SI, there are insufficient data available to conclude that SI viruses have any specific association with these syndromes.10

Pathology

The gross lesions found in uncomplicated acute SI are mainly those of a viral pneumonia. In severe cases the mucosa of the nasal turbinates, pharynx, larynx, trachea and large bronchi may be hyperaemic, swollen and covered by a tenacious exudate that may be blood-tinged, fibrinous or mucopurulent.10 Some of the smaller bronchi and bronchioles may be distended and occluded by the exudate which results in lobular atelectasis of the lungs. Gross lung lesions appear as sharply demarcated dark red or purple areas of consolidation, mainly in the cranioventral parts.3 Lung oedema may be present.

Microscopically, necrosis of epithelial cells of the alveoli with subsequent sloughing of affected cells occurs between 24 and 96 hours after experimental infection and is associated with alveolar oedema and diffuse interstitial pneumonia (initially mainly neutrophilic, but subsequently histiocytic) which increase the air–blood–tissue barrier by 85 per cent within 96 hours of infection.39 Peribronchial and perivascular neutrophil and mononuclear cell infiltration have also been observed, as well as numerous polymorphonuclear granulocytes in septal capillaries, and platelet aggregates in septal capillaries associated with sites of endothelial swelling and detachment.3, 39 At 24 hours after experimental infection, occasional type I pneumocytes contain both intracytoplasmic and intranuclear inclusions. From this observation it has been inferred that viral replication interferes not only with surfactant production and release in type II pneumocytes but also with regeneration of type I pneumocytes.39 A severe proliferating and necrotizing pneumonia in pigs in which an influenza infection was involved was described in 1990 in Canada.23

Diagnosis and differential diagnosis

Swine influenza should be suspected whenever there is a sudden onset of a respiratory disease with high morbidity in a piggery. However, an aetiological diagnosis requires laboratory assistance because subclinical infections may occur and clinical signs are not always typical.24 Virus isolation and serological techniques for the diagnosis of swine influenza are similar for those in other species (equine, avian and human). While the SI viruses have been cultivated in many cell-culture systems, the chicken egg embryonated for 10 days remains a highly reliable and economical system for the isolation of these viruses (see Equine influenza). The specimen of choice for viral isolation from a live animal is nasal or pharyngeal mucus or exudate taken during the early febrile period.10

Conditions which may be confused with SI are porcine pleuropneumonia, pasteurellosis, enzootic pneumonia, inclusion body rhinitis and non-fatal cases of pseudorabies in adult animals. Hog cholera, African swine fever and septicaemic bacterial infections (e.g. erysipelas and salmonellosis) should be considered when erythema is evident.

Control

Standard biosecurity measures to prevent contact between susceptible and infected animals are appropriate for preventing SI infections (see Epidemiology). Because of the potential for interspecies transfer of influenza viruses biosecurity measures should include preventing contact with avian species. Any human beings suspected of having influenza should be excluded from contact with pigs. Inactivated whole virus or split-product vaccines containing H1N1 and H3N2 components are commercially available and commonly used in Europe.10

References

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