INFLUENZA IN AQUATIC MAMMALS
Leslie a. Reperant1, albert d.m.e. Osterhaus2 AND THIJS KUIKEN2
1Department of Virology, Erasmus MC, Rotterdam, The Netherlands
2Department of Virology, Erasmus MC, and Artemis Research Institute for Wildlife Health in Europe, Rotterdam, The Netherlands
Although there is evidence of both influenza A and influenza B virus infections in several species of marine mammals, only influenza A virus infections are known to have caused disease.
EPIDEMIOLOGY
In Europe, serologic evidence of exposure to influenza A viruses has been reported in one seal (species not specified) from the North Sea in 1988 (LPAIV of the H4 subtype), and in harp seals (Pagophilus groenlandicus) and hooded seals ( Cystophora cristata) from the Barents Sea in 1991 and 1992 (subtype not determined)(58,59). Influenza B viruses were isolated from harbour seals (Phoca vitulina) from the North Sea in 1999, and antibodies against the virus were detected in North Sea harbour seals and grey seals (Hali- choerus grypus) between 1995 and 1999(3).
Outbreaks of disease caused by influenza A viruses in marine mammals occurred along the New England coast of the USA. Influenza A viruses of different subtypes (H7N7, H4N5, H4N6 and H3N3) were isolated from stranded harbour seals in 1979, 1982, 1991 and 1992, respec- tively(60-62). In addition, LPAIV H13N2 and H13N9 viruses were isolated from a pilot whale (Globicephala melas) in 1984 near Maine, when major strandings were reported(63).
Only harbour seals and a pilot whale ( Globicephela spp.) are known to have developed disease following infection with influenza A virus. LPAIV H1N3 were isolated from lung and liver samples of minke whales (Balaenoptera acutorostrata) collected in 1975 and 1976 in the South Pacific(64), but no details were provided on clinical signs or lesions in infected animals.
Influenza B virus, which infects mostly humans, has been isolated from harbour seals, but it is unclear whether the virus causes clinical disease in this species.I n addition to harp seals, hooded seals, harbour seals and grey seals from European waters (see above), antibodies against avian and human influenza A viruses and influenza B viruses were also reported in Kuril harbour seals (Phoca vitulina stejnegeri) near Japan, in ringed seals (Pusa hispida) from Alaska and the Kara Sea, in Caspian seals (Pusa caspica), in Baikal seals (Pusa sibirica) and in sea lions (species not specified) from the Bering Sea(2’65). Antibodies against influenza A viruses were detected in belugas (D el- phinapterus leucas) from Arctic Canada, and common minke whales and Dall’s porpoises (Phocoenoides dallι) from the western North Pacific and Antarctic Oceans1-66’67). Further determination of the subtypes was either not possible or unsuccessful.
Little is known on the epidemiology of influenza A viruses in marine mammals. In North America, influenza A outbreaks in harbour seals typically occurred during late winter.
Marine mammals are considered accidental hosts for avian and human influenza viruses. However, influenza viruses can remain in seal populations for several months to several years. The outbreak of LPAIV H7N7 infection in North American harbour seals in 1979 lasted 10 months)60). Likewise, LPAIV H4N5 isolated in North American harbour seals in winter 1983 was virtually identical to a virus isolated from the lungs of an emaciated seal found dead in June 1982, indicating that this virus may have been sustained for more than a year in the seal popu- lation)61). In spring 1999, harbour seals from the North Sea were found infected with an influenza B virus closely related to strains that had circulated in humans several years earlier. Antibodies against this virus were found in archived sera of stranded harbour seals and grey seals )Hal- ichoerus grypus), collected between 1995 and 1999.
Together, these results suggest that the virus had circulated in seal populations for several years)3).All influenza A viruses isolated from marine mammals are of avian origin, demonstrating cross-species transmission of LPAIV from birds to marine mammals)2). Seabirds and pinnipeds frequently share habitats at roosting or haul-out sites, probably favouring cross-species transmission of LPAIV. Likewise, cetaceans may have close contact with seabirds at sea. They both feed concurrently on the same fish species, which may facilitate cross-species transmission. The detection of antibodies against LPAIV in different seal species further supports frequent cross -species transmission from wild birds to pinnipeds. Furthermore, the detection of antibodies against human influenza A and B viruses and isolation of influenza B viruses in seals indicates cross-species transmission of influenza viruses from humans to pinnipeds)3).
Once introduced into marine mammals, only influenza A viruses caused outbreaks of disease in harbour seals, which suggests seal-to-seal transmission, probably via the respiratory route. Some LPAIV isolated from infected seals behaved more like mammalian influenza A viruses, as they replicated better in mammalian than in avian species, suggesting that LPAIV may have adapted to mammalian hosts once introduced into seals)68).
PATHOGENESIS, PATHOLOGY
AND IMMUNITY
Little is known about the pathogenesis of influenza virus infection in marine mammals. In harbour seals, LPAIV typically have a restricted tissue tropism for the respiratory tract, and are most frequently isolated from the lungs of infected animals. However, LPAIV were occasionally isolated from the brain of naturally infected seals, indicating that LPAIV can spread beyond the respiratory tract in this species)61). LPAIV H7N7 were also isolated from the bronchial lymph node and from the third eyelid of experimentally infected harbour seals)68), and LPAIV H4N5 from bronchial, mesenteric and mandibular lymph nodes as well as corneal swabs of harbour seals, ringed seals and harp seals)61).
In the pilot whale infected with LPAIV near Maine, USA, viruses were isolated from the lungs and hilar lymph node)63), also demonstrating a preferred tropism for the respiratory tract in this species.Necrotizing bronchitis and bronchiolitis, and haemorrhagic interstitial pneumonia were reported on post mortem examination of harbour seals that died of natural influenza A virus infection)60-62). Lesions were absent or similar in experimentally infected seals, and co- infection, e.g. with Mycoplasma, is thought to have contributed to more severe disease in naturally infected seals)61,68).
Harbour seals, ringed seals and harp seals experimentally infected with a seal isolate of LPAIV H4N5 had detectable antibodies 2 weeks post-infection, declining by day 30 post-infection)61). Sera from harbour seals caught along the New England coast of the USA collected at the end of the seal epidemic of 1979-1980 had detectable levels of antibodies against the H7N7 virus)68).
CLINICAL SIGNS
In North America, influenza A virus infection in harbour seals resulted in massive outbreaks of fatal respiratory disease)2). Approximately 600 seals, representing about 25% of the local population, died of LPAIV H7N7 infection between December 1979 and October 1980)60), and another outbreak of fatal respiratory disease caused by LPAIV H4N5 resulted in a three- to four-fold increase in seal mortality between January and March 1983)61). Strandings of harbour seals increased in winter 1991 and winter 1992, when LPAIV H4N6 and H3N3, respectively, were isolated from dead animals)62).
Clinical signs of influenza A virus infection in harbour seals included prostration, respiratory distress, mucopurulent to haemorrhagic oculo-nasal discharge and subcutaneous emphysema, resulting in a swollen neck and quivering of the muscles1-60-62). The disease developed within 2 to 3 days following infection, and some animals died within hours after feeding normally)60’68).
Experimental infection of harbour seals, ringed seals and harp seals with viruses isolated from fatal cases typically resulted in subclinical infection or milder but similar disease. Whereas harbour seals, ringed seals and harp seals experimentally infected with a seal isolate of LPAIV H4N5 did not develop disease)61), mild cough and mucopurulent oculo-nasal discharge were observed in harbour seals experimentally infected with the seal isolate of LPAIV H7N7)68). In the pilot whale infected with LPAIV near Maine, USA, clinical signs were non-specific and included skin sloughing and extreme emaciation. The animal had difficulties swimming, diving and surfacing)63).To date, influenza A viruses have not been associated with disease outbreaks in European seals. Influenza B virus was isolated from the throat swab of a juvenile harbour seal with respiratory problems in spring of 1999)3). However, the seal was probably also infected with lungworms, and it remains unknown whether the virus was the aetiological cause of the respiratory signs.
DIAGNOSIS
The methods used for the diagnosis of avian influenza in birds can be applied to marine mammals.
MANAGEMENT AND CONTROL
No management and control measures are required.
PUBLIC HEALTH CONCERN
Five humans who handled seals infected with LPAIV H7N7 developed conjunctivitis, associated with high titres in their conjunctival swabs, demonstrating the zoonotic potential of the virus)69). Precautions, such as wearing protective clothing and glasses, should be applied during necropsy of infected marine mammals.
SIGNIFICANCE AND IMPLICATIONS FOR ANIMAL HEALTH
LPAIV outbreaks may cause significant morbidity and mortality in harbour seals and potentially other marine mammals. In addition, there is evidence of cross- species transmission of influenza viruses of human origin to pinnipeds, although their pathogenicity for pinnipeds is unknown.