infectious salmon anaemia
- Host Animals
- Hosts/Species Affected
- Distribution Table
- List of Symptoms/Signs
- Disease Course
- Impact Summary
- Impact: Economic
- Impact: Environmental
- Zoonoses and Food Safety
- Links to Websites
- Distribution Maps
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PicturesTop of page
IdentityTop of page
Preferred Scientific Name
- infectious salmon anaemia
International Common Names
- English: infectious salmon anemia
OverviewTop of page
Infectious salmon anaemia (ISA) is a viral disease of farmed Atlantic salmon (Salmo salar L.) recognized for the first time in Norway in 1984 (Thorud and Djupvik., 1988), and is caused by the orthomyxovirus infectious salmon anaemia virus (ISAV) (Falk et al., 1997; Krossøy et al., 1999; Mjaaland et al., 1997). The disease may appear as a systemic and lethal condition characterised by severe anaemia and haemorrhages in several organs. Early attempts to isolate the causative virus in commercial fish cell lines were not successful until the establishment of a new cell line (SHK-1) from Atlantic salmon head kidney (Dannevig et al., 1995).
Since its first recognition in Norway, ISA has been reported to occur in several countries surrounding the North Atlantic ocean, both in North America and within the UK (Bouchard et al., 2001; Lovely et al., 1999; Rodger et al., 1998). Atlantic salmon is the only susceptible fish species known to develop the disease, but ISAV has been detected in wild salmonids (Raynard et al., 2001) and in a few marine species collected close to ISA-infected sites (MacLean et al., 2003).
Mortality may vary greatly within and between different netpens in a seawater fish farm as well as between different fish farms, and the cumulated mortality in single netpens may range from 10% to 90%. The infection spreads rather slowly between netpens within a fish farm.
The disease is characterized by severe anaemia and haemorrhages in several organs. Before the isolation and identification of the causative agent, the diagnosis of ISA was based on clinical signs, pathology and histopathology which at that time was considered as typical for ISA. The isolation of ISAV in cell culture has improved the diagnosis of ISA significantly. Diagnostic methods for detection of virus antigens or nucleic acids in tissue samples are now in use in several laboratories worldwide.
[Based upon material originally published in Woo PTK, Bruno DW, eds., 1999. Fish diseases and disorders, Vol. 3 Viral, bacterial and fungal infections. Wallingford, UK: CABI Publishing.]
Host AnimalsTop of page
|Animal name||Context||Life stage||System|
|Gadus morhua (Atlantic cod)||Wild host|
|Oncorhynchus keta (chum salmon)||Experimental settings|
|Oncorhynchus kisutch (coho salmon)|
|Oncorhynchus mykiss (rainbow trout)||Experimental settings, Subclinical|
|Oncorhynchus tshawytscha (chinook salmon)||Experimental settings|
|Pollachius virens||Wild host|
|Salmo salar (Atlantic salmon)||Domesticated host, Experimental settings, Subclinical, Wild host||Aquatic: Adult||Enclosed systems/Cages|
|Salmo trutta (sea trout)||Experimental settings, Subclinical|
|Salvelinus alpinus (Arctic charr)||Experimental settings, Subclinical|
Hosts/Species AffectedTop of page
In Atlantic salmon, disease outbreaks occur mainly in the sea water stage. Farmed Atlantic salmon parr kept in fresh water did however, develop ISA following experimental infection (Dannevig et al., 1993), and a few clinical cases have been reported in fresh water hatcheries, including one case in yolk sac fry (Nylund et al., 1998).The influence of sea water could not be excluded for these cases.
Wild Atlantic salmon are susceptible to ISA and show the same clinical signs as farmed fish after intraperitoneal injection of ISA-infective material (Nylund et al., 1995c). Replication of ISAV has been demonstrated in experimentally infected brown trout and anadromous sea trout (Salmo trutta L.), and rainbow trout (Oncorhynchus mykiss) (Nylund et al., 1995a; Nylund and Jakobsen, 1995; Nylund et al., 1997). ISAV has been detected by reverse transcription polymerase chain reaction (RT-PCR) in experimentally infected Arctic charr (Salvelinus alpinus), but virus replication in this species has not been demonstrated (Snow et al., 2001). None of these species develop any clinical signs of ISA.
In 2001, clinical ISA was reported in Coho salmon (Oncorhynchus kitsutch) in Chile although the pathological lesions differed from ISA in Atlantic salmon (Kibenge et al., 2001a). However, in a challenge trial, various Canadian and Norwegian ISAV strains were injected intraperitoneally into Pacific salmon species (O. mykiss, O.keta, O. kitsutch, O. tshawytscha) (Rolland and Winton, 2003). Virus could be re-isolated, but did not cause ISAV-related mortality. The authors concluded that Pacific salmon are quite resistant to ISAV compared to Atlantic salmon, but that these species should not be ignored as potential virus carriers.
It has been reported that ISAV is able to propagate in herring after bath challenge, and this species may therefore be an asymptomatic carrier of the virus (Nylund et al., 2002). Using RT-PCR, Raynard et al. (2001) provided evidence that ISAV is present in feral Atlantic salmon and sea trout along the Scottish coast. They did not however isolate ISAV nor detect any PCR-positive fish out of 1447 non-salmonids.
In a comprehensive survey, alewife (Alosa pseudoharengus), American eel (Anguilla rostrata), Atlantic herring (Clupea harengus harengus), Atlantic mackerel (Scomber scombrus), Atlantic cod (Gadus morhua), haddock (Melanogrammus aeglefinus), Atlantic halibut (Hippoglossus hippoglossus), pollock (Pollachius virens), American shad (Alosa sapidissima) and winter flounder (Pseudopleuronectes americanus) were screened for ISAV using RT-PCR. Cod and pollock sampled in the vicinity of ISA-diseased salmon tested positive for ISAV (MacLean et al., 2003). Pollock cohabitating with farmed Atlantic salmon in sea cages, remained RT-PCR negative when harvested together with salmon experiencing increased mortality due to ISA (McClure et al., 2004). The same species was negative for ISAV following exposure by intraperitoneal injection of virus or by cohabitation with ISAV-infected Atlantic salmon (Snow et al., 2002).
Clinical ISA has so far not been detected in any marine fish species. There are no indications that ISAV can infect mussel (Mytilus edulis) and scallops (Pecten maximus) or that these shellfish play any role as reservoir for ISAV (Bjørshol et al., 1999).
DistributionTop of page
Natural outbreaks of ISA have been recorded in Norway since 1984. For several years the disease was only diagnosed in Norway, but in 1996, a disease in Canada called hemorrhagic kidney syndrome was verified as ISA . ISA was for the first time diagnosed in Scotland in 1998 and thereafter also in the Shetland Islands (Murray, 2003). In 2000 it appeared in the Faroe Islands and in 2001 at the eastern coast of the USA . ISAV has also been isolated from Coho salmon in Chile and from rainbow trout in Ireland (OIE, 2003).
Distribution TableTop of page
The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.Last updated: 10 Jan 2020
|Continent/Country/Region||Distribution||Last Reported||Origin||First Reported||Invasive||Reference||Notes|
|Lesotho||Absent, No presence record(s)||OIE (2009)|
|Sudan||Absent, No presence record(s)||OIE (2009)|
|Tunisia||Absent, No presence record(s)||OIE (2009)|
|Armenia||Absent, No presence record(s)||OIE (2009)|
|Azerbaijan||Absent, No presence record(s)||OIE (2009)|
|Bahrain||Absent, No presence record(s)||OIE (2009)|
|Bangladesh||Absent, No presence record(s)||OIE (2009)|
|China||Absent, No presence record(s)||OIE (2009)|
|Indonesia||Absent, No presence record(s)||OIE (2009)|
|Iraq||Absent, Unconfirmed presence record(s)||OIE (2009)|
|Israel||Absent, No presence record(s)||OIE (2009)|
|Japan||Absent, No presence record(s)||OIE (2009)|
|Kazakhstan||Absent, No presence record(s)||OIE (2009)|
|Kuwait||Absent, No presence record(s)||OIE (2009)|
|Kyrgyzstan||Absent, No presence record(s)||OIE (2009)|
|Malaysia||Absent, No presence record(s)||OIE (2009)|
|Singapore||Absent, No presence record(s)||OIE (2009)|
|Austria||Absent, No presence record(s)||OIE (2009)|
|Belarus||Absent, No presence record(s)||OIE (2009)|
|Croatia||Absent, No presence record(s)||OIE (2009)|
|Cyprus||Absent, No presence record(s)||OIE (2009)|
|Czechia||Absent, No presence record(s)||OIE (2009)|
|Denmark||Absent, No presence record(s)||OIE (2009)|
|Faroe Islands||Present||Office International des Epizooties (2003)|
|Finland||Absent, No presence record(s)||OIE (2009)|
|France||Absent, No presence record(s)||OIE (2009)|
|Germany||Absent, No presence record(s)||OIE (2009)|
|Hungary||Absent, No presence record(s)||OIE (2009)|
|Iceland||Absent, No presence record(s)||OIE (2009)|
|Ireland||Absent, No presence record(s)||OIE (2009); Office International des Epizooties (2003)|
|Latvia||Absent, No presence record(s)||OIE (2009)|
|Lithuania||Absent, No presence record(s)||OIE (2009)|
|Netherlands||Absent, No presence record(s)||OIE (2009)|
|Norway||Present||OIE (2009); CABI (Undated)|
|Poland||Absent, No presence record(s)||OIE (2009)|
|Portugal||Absent, No presence record(s)||OIE (2009)|
|Slovakia||Absent, No presence record(s)||OIE (2009)|
|Slovenia||Absent, No presence record(s)||OIE (2009)|
|Spain||Absent, No presence record(s)||OIE (2009)|
|Sweden||Absent, No presence record(s)||OIE (2009)|
|Switzerland||Absent, No presence record(s)||OIE (2009)|
|Ukraine||Absent, No presence record(s)||OIE (2009)|
|United Kingdom||Absent, No presence record(s)||OIE (2009); CABI (Undated)|
|Belize||Absent, No presence record(s)||OIE (2009)|
|Canada||Absent, Unconfirmed presence record(s)||OIE (2009)|
|-New Brunswick||Present||Byrne et al. (1998); Office International des Epizooties (2003); CABI (Undated)|
|-Nova Scotia||Present||Kibenge et al. (2001); Office International des Epizooties (2003)|
|Costa Rica||Absent, No presence record(s)||OIE (2009)|
|Cuba||Absent, No presence record(s)||OIE (2009)|
|Greenland||Absent, No presence record(s)||OIE (2009)|
|Guatemala||Absent, No presence record(s)||OIE (2009)|
|Mexico||Absent, No presence record(s)||OIE (2009)|
|Nicaragua||Absent, No presence record(s)||OIE (2009)|
|United States||Absent, No presence record(s)||OIE (2009)|
|-Maine||Present||CABI (Undated)||Original citation: Bouchard and et al. (2001)|
|Australia||Absent, No presence record(s)||OIE (2009)|
|French Polynesia||Absent, No presence record(s)||OIE (2009)|
|New Caledonia||Absent, No presence record(s)||OIE (2009)|
|New Zealand||Absent, No presence record(s)||OIE (2009)|
|Argentina||Absent, No presence record(s)||OIE (2009)|
|Brazil||Absent, No presence record(s)||OIE (2009)|
|Chile||Present||OIE (2009); CABI (Undated)|
|Colombia||Absent, No presence record(s)||OIE (2009)|
|French Guiana||Absent, No presence record(s)||OIE (2009)|
PathologyTop of page
A characteristic finding in ISA is that moribund fish are severely anaemic and haematocrit values below 10 are common in the terminal stage. When the haematocrit is that low, circulatory disturbances are usually observed in several organs. The previously described ISA-typical dark liver may be observed, but is not always a consistent finding.
The most prominent external signs of the acute form of ISA are pale gills, exophthalmus and sometimes haemorrhages in the eye chamber and on the skin, and scale oedema may occur. The principal macroscopically pathological features include ascites, liver partly or diffusely dark red, dark and swollen spleen, and congested and dark intestinal wall as well as petechiae in the adipose tissue and swimbladder (Thorud and Djupvik, 1988; Evensen et al., 1991).
The major histopathological finding is multifocal haemorrhagic liver necrosis that may become confluent (Evensen et al., 1991) . The lesions result in extensive congestion of the liver with dilated sinusoids and in later stages, the appearance of blood-filled spaces. By electron microscopy of experimentally infected fish, changes involving the perisinusoidal macrophages were observed from day 4 p.i. (Speilberg et al., 1995). At day 14 p.i., degenerative features of the sinusoidal endothelium were observed, and by day 18 p.i., areas of the liver were devoid of a sinusoidal endothelial lining. Gross and light microscopic changes were first recorded at day 18 p.i., as was a significant decrease in the haematocrit values. By day 25 p.i., characteristic multifocal, confluent, haemorrhagic necroses were present (Speilberg et al., 1995). The ISA-typical gross macroscopic liver changes thus become present late in the disease development.
In ISA outbreaks at the American East coast in the late 1990s the pathological changes were dominated by microscopic findings in the kidney. The major pathological findings included renal interstitial haemorrhage with tubular necrosis and casts, branchial lamellar and filamental congestion and congestion of the intestine and pyloric caeca (Byrne et al., 1998). The disease therefore became known as haemorrhagic kidney syndrome (HKS). Perivascular inflammation was a common finding in the livers examined (Byrne et al., 1998). Gross examination of the fish appeared somewhat similar to the reports of ISA from Norway. However, in the fish from outbreaks in New Brunswick, gross liver congestion was a rare finding (Byrne et al., 1998; Mullins et al., 1998; O'Halloran et al., 1999) . HKS was confirmed as ISA using RT-PCR and cell culture followed by an indirect fluorescent antibody test (IFAT) (Lovely et al., 1999) Interestingly, gross hepatic congestion of ISAV-infected fish has become a more common finding in New Brunswick (Mullins et al., 1998). Recently, the kidney and intestinal manifestations of the disease have also been recognized in Norway (Dale et al., 2005).
In the chronic form of ISA, the signs are more diffuse and can be difficult to interpret. The liver may appear pale or yellowish and the anaemia may not be as severe as in the acute disease. Furthermore, there is less ascitic fluid, but haemorrhages in the skin and swim bladder and oedema in the scale pockets and swim bladder may be more pronounced than in acutely diseased fish (Evensen et al., 1991). This classification, however, is not absolute and variation in the pathological changes and the severity of these has recently become more evident.
The ability to demonstrate the presence of ISAV has been the decisive diagnosis of the disease. In some instances some of the pathological changes are expressed to a greater extent than usual, while other pathological changes are totally or partly lacking.
DiagnosisTop of page
Diagnosis of ISA was initially based on typical pathological changes, including macroscopic signs and histological and haematological findings (for details see Evensen et al., 1991; OIE, 2003). A dark liver was considered as a necessary finding, while other macroscopic signs supported the diagnosis. The presence of multifocal, haemorrhagic liver necrosis with a 'zonal' appearance and haematocrit values below 10% confirmed the diagnosis. Following the isolation of ISAV in 1995 (Dannevig et al., 1995) a number of methods for detection of virus in tissue samples have been established, which have improved the diagnosis of subacute and chronic forms of ISA and of carriers. These methods include detection of viral antigens in tissue imprints (Falk et al., 1998) or in fixed sections by immunostaining, isolation of ISAV in cell culture (Dannevig et al., 1995), including immunostaining of cells for identification of virus (Falk et al., 1998), and detection of viral RNA by PCR-based techniques (Devold et al., 2000; Mikalsen et al., 2001; Mjaaland et al., 1997).
Outbreaks of ISA are usually associated with increased mortality, but great variation in daily mortality are seen. Infected fish appear lethargic and may keep close to the walls of the net-pen. In terminal stages, diseased fish are often at the bottom of the cage. The most prominent external signs are gill pallor and haemorrhage in the anterior eye chamber. Exophthalmia is seen often.
The major internal gross pathological changes are ascites, congestion of liver and spleen, petechiae in visceral fat and, in some cases, congestion of the foregut. The liver may appear partly or diffusely dark red, and a fibrinous layer may cover the liver capsule. The stomach may be distended by a serous/viscous fluid, and streaky haemorrhages in the mucosa of the stomach can be seen. Occasionally, haemorrhages in skeletal muscle occur.
Haematocrit <10 in the end stages is the most typical haematological finding. Values in the range of 25-30 are often seen in less severe cases.
The following histological findings may be consistent with ISA, but none of the lesions is pathognomonic to ISA: numerous erythrocytes in central venous sinus and lamellar capillaries of the gills, haemorrhages (multifocal to confluent) and/or necrosis of hepatocytes at some distance from large vessels in the liver, accumulation of erythrocytes in blood vessels of the intestinal lamina propria and haemorrhage into the lamina propria may occur, accumulation of erythrocytes and distention of stroma in the spleen, interstitial haemorrhage in the kidneys with tubular necrosis in the haemorrhagic areas and accumulation of erythrocytes in the kidney glomeruli (Evensen et al., 1991; OIE, 2003).
Detection of ISAV in tissue samples
ISAV can be detected in kidney imprints from Atlantic salmon exhibiting clinical signs of ISA using an immunofluorescence antibody techinique (IFAT) with anti-ISAV haemagglutinin-esterase (HE) MAb (Falk et al., 1998) as the primary antibody. Antibodies suitable for immunohistochemistry have recently been developed, and are currently being evaluated for diagnostic use. These techniques may not be sensitive enough for detection of ISAV in subclinical infections.
The first isolation of ISAV was in the salmonid cell line SHK-1 (Dannevig et al., 1995), but other salmonid cell lines such as CHSE-214 (Kibenge et al., 2000), ASK (Devold et al., 2000) and TO (Wergeland and Jakobsen, 2001) may also support viral propagation. Strain variations with respect to cell susceptibility have been observed. The CHSE-214 cell line does not seem to be susceptible to European variants of ISAV (Kibenge et al., 2000). The virus may be identified using IFAT on infected cell cultures (Falk and Dannevig, 1995; Falk et al., 1998).
The Atlantic salmon cell lines SHK-1 (Dannevig et al., 1995), TO (Wergeland and Jakobsen, 2001) and ASK-2 (Devold et al., 2000; Rolland et al., 2003) all support growth of the virus. There are however some indications that these cells do not support growth of all isolates, as virus from some RT-PCR-positive samples does not survive in these cells (Kibenge et al., 2000; Mjaaland et al., 2002a; Rimstad and Mjaaland, 2002). The CHSE-14 cell line supports the growth of some ISAV isolates, resulting in high titres and profound cytopathic effect, while other isolates are non-cytopathic (Kibenge et al., 2000), and some do not replicate in this cell line at all (Kibenge et al., 2004; Munir and Kibenge, 2004), thereby limiting its utility in virus isolation. It seems that currently available fish cell lines are either not sensitive enough or are not permissive for all ISAV strains (reviewed by Kibenge et al., 2004)
The first PCR-based method for detection of ISAV RNA was described in 1997 (Mjaaland et al., 1997). Though the techniques for performing RT-PCR have been optimized since then (Mikalsen et al., 2001), the first described primer sets from genomic segment 8 for use in ISAV RT-PCR are still in use in several laboratories. Other primer sets from segments 8 (Devold et al., 2000) and 6 (Inglis et al., 2000) have been described and found useful for detection of ISAV by RT-PCR. The applicability of this technique in the diagnosis of ISA has been discussed by Mjaaland et al. (2002b). The use of real-time RT-PCR in diagnosis of viral diseases has increased considerably in the last decade, and has also been established for ISAV (Munir and Kibenge, 2004). The specificity and probably also the sensitivity may be higher than for conventional RT-PCR, especially when including a sequence-specific probe.
List of Symptoms/SignsTop of page
|Finfish / Build up of bloody fluids - Body Cavity and Muscle||Aquatic:All Stages||Sign|
|Finfish / Fish sinking to bottom - Behavioural Signs||Aquatic:All Stages||Sign|
|Finfish / Generalised lethargy - Behavioural Signs||Aquatic:All Stages||Sign|
|Finfish / Hepatomegaly - liver swelling / oedema - Organs||Aquatic:All Stages||Sign|
|Finfish / Liver - white / grey patches (haemorrhage / necrosis / tissue damage) - Organs||Aquatic:All Stages||Sign|
|Finfish / Mortalities -Miscellaneous||Aquatic:All Stages||Sign|
|Finfish / Paleness - Gills||Aquatic:All Stages||Sign|
|Finfish / Pop-eye - Eyes||Aquatic:All Stages||Sign|
|Finfish / Splenomegaly - spleen swelling / oedema - Organs||Aquatic:All Stages||Sign|
Disease CourseTop of page
Pathogenesis and immunity
Before the introduction of legislatory regulations for ISA in Norway in the beginning of the 1990s, the cumulative mortality during an outbreak could exceed 90% although it more normally varied from insignificant to moderate. This variation is influenced by: a) the genetics of the fish, i.e. experimental trials with smolts from different farms or genetic backgrounds showed variations in mortality between 10 and 100% (Grimholt et al., 2003; Nylund et al., 1995c); b) virus strain (Mjaaland et al., 2002a); c) management practices, i.e. disease outbreaks often occur subsequent to a stress situation.
The incubation time is usually between 10 and 20 days after intraperitoneal injection of ISAV (Dannevig et al., 1994; Rimstad et al., 1999; Totland et al., 1996). In a naturally infected population of farmed fish, some individuals may harbour the virus for weeks or months before development of the disease (Rimstad et al., 1999). Prior to an outbreak, a slightly increased mortality is often seen. The disease outbreak may be observed as a rise in mortality developing within 1-3 weeks and is often related to a stress situation. The outbreak is usually restricted to one or two netpens, which indicates that the mere presence of ISA virus is not enough to induce a disease outbreak. Classical ISA-affected fish appear lethargic, and in terminal stages diseased fish often sink to the bottom of the cage. The further development of the disease varies, and up to 12 months can pass before clinical ISA has spread to neighbouring netpens in a fish farm (Vågsholm et al., 1994). The signs exhibited by infected fish range from none to severe, depending on factors such as infective dose, temperature, season, age, immune status and virus strain. The disease appears throughout the year, although earlier reports from Norway recorded most outbreaks in early summer, while a minor peak was observed in November (Vågsholm et al., 1994). Two main forms of ISA outbreaks have been described: acute form, with rapid development and high mortality, and chronic form, in which a slow increase in mortality can be observed during several months.
The categorization of disease outbreaks into "acute" and "protracted" is, however, a simplification, as the course of disease development, clinical signs, and histopathology varies between ISA outbreaks, and transitional forms are often present (Bouchard et al., 1999; Lovely et al., 1999; Mullins et al., 1998).
Studies of the mechanisms of ISAV infection indicate that the major port of ISAV entry is the gills, but oral entry cannot be excluded (Mikalsen et al., 2001). Experiments in which the tested fish were infected from ISAV-infected cohabitant fish showed that the virus spread through the body, as tested by RT-PCR in several different organs, and began to increase at 5 days post exposure (Rimstad et al., 1999). Viral load peaked at 15 days and was followed by a temporary decrease with a minimum at around 25 days p.i. However, the virus was not cleared, and after 25 days, a second rise in viral replication followed which continued to the terminal stage of ISA (Mikalsen et al., 2001; Rimstad et al., 1999).
Endothelial cells are the main target cells for ISAV (Hovland et al., 1994), and the virus is found budding from such cells (Koren et al., 1997). The ubiquitous presence of endothelial cells enables the virus to produce a systemic infection (Gregory, 2002; Rimstad et al., 1999). By in situ hybridization the most prominent ISAV-specific signals were obtained from the endothelial cells of heart tissue (Gregory, 2002). The presence of virus in other cell types, including leukocytes, has been reported (Dannevig et al., 1994; Nylund et al., 1995b), and indications of replication of ISAV in such cells have been reported (Dannevig and Falk, 1994; Sommer et al., 1996).
ISAV specifically binds to glycoproteins containing 4-O-acetylated sialic acids, and the viral esterase specific for 4-O-acetylated sialic acids hydrolyses ISAV receptors, indicating that this sialic acid represents a receptor determinant for ISAV (Hellebø et al., 2004). ISAV infects cells via the endocytic pathway and the fusion between virus and cell membrane takes place in the acid environment of endosomes (Eliassen et al., 2000). Although indications of antibody-enhanced (rabbit antisera) uptake of ISAV in fish cell lines have been presented (Joseph et al., 2003), this is of unknown function in vivo. For transcription and expression of ISAV proteins, 8-18 nucleotide 5'-cap structures are cleaved from cellular heteronuclear RNAs (cap-stealing), and the mRNA is polyadenylated from a signal 13-14 nucleotides downstream of the 5'-end terminus of the vRNA (Sandvik et al., 2000). Cap-stealing is a process that orthomyxoviruses perform in the nucleus. This process affects the natural transcription and protein expression of the cell and thus is an important factor in the outcome of the infection. The IFN type I inducer poly I:C induces no or only minor protection against ISAV infection in TO or SHK-1 cells (Jensen and Robertsen, 2002), indicating that ISAV has developed an efficient IFN type I antagonistic response. Budding has been observed from endothelial cells (Koren and Nylund, 1997), and the ISAV esterase specificity for 4-O-acetylated sialic acids is thought to be important in the release from the host cell.
The pathogenesis, or disease outcome, is dependent on the immune response of the host and viral virulence properties. Recent infection experiments indicate that a cellular response, measured as a virus-induced proliferative response of leukocytes, correlate with survival and virus clearance, while induction of a humoral response is less protective. It has been discussed whether the determinant of viral virulence is associated with the hyper polymorph-region of the haemagglutinin-esterase protein, juxtaposed to the membrane. Full-length variants of the HE are considered least virulent (Cook-Versloot et al., 2004; Cunningham et al., 2002; Nylund et al., 2003).
EpidemiologyTop of page
Horizontal transmission has been demonstrated in cohabitation experiments, indicating that water-borne transmission is important for the spread of ISA (Thorud and Djupvik, 1988). The virus may be shed into the water by various routes, such as skin, mucus, faeces and urine (Totland et al., 1996), and the authors suggest that the most likely route of virus entry is through the gills and skin injuries. Transmission by coprophagy has also been proposed (Nylund et al., 1994).
ISAV may survive a substantial time in seawater, depending on temperature and its association to organic matter. No significant loss in virus titre was observed after incubation of virus supernatants for 14 days at 4°C and 10 days at 15°C (Falk et al., 1997), and by means of transmission experiments it has been shown that infectivity of tissue preparations is retained for at least 48 h at 0°C, 24 h at 10°C and 12 h at 15°C (Torgersen, 1998). However, the survival time of ISAV in sea water may be shorter. It is difficult to estimate exactly how long the virus may remain infectious in the natural environment because the presence of particles or substances may bind or inactivate the virus. Infection experiments have shown that tissue preparations from ISA-diseased fish remain infectious for at least 20 h in sea water at 6°C (Nylund et al., 1994).
The introduction of ISAV to a sea site is mainly associated with smolt transfer, transport of infected adult fish between fish farms, horizontal spreading from nearby infected farms and release of untreated water into the sea from nearby processing plants (Jarp and Karlsen, 1997; Vågsholm et al., 1994). Murray et al. (2002) also demonstrated a link between farm contamination and vessels moving fish between sites and transporting harvest.
The incidence of ISA may be greatly reduced by implementation of general hygiene legislation regarding the movement of fish, mandatory health control, and slaughterhouse and transport regulations, as well as specific measures including slaughtering and restrictions on neighbouring farms.
The sea louse (Lepeophtheirus salmonis) has been suggested as a possible vector for ISAV, as Atlantic salmon exposed to sea lice which were removed from ISA-infected fish developed ISA (Nylund et al., 1993, 1994). Whether this route of transmission represents a passive transfer of virus or is due to active replication of virus in the sea lice has not been clarified.
In general, vertical transmission of virus may occur by transfer of virus located intracellularly in eggs or sperms or by transfer of virus adsorbed on the external surface of these cells. Little is known about the ISAV status in the broodstock population or whether infective virus can be transmitted to the next generation through sexual products. Keeping in mind that fry are just as susceptible to ISA as fish in seawater, there are no field observations so far that confirm that ISAV is transmitted vertically. Experimentally infected ISAV-positive broodstock without clinical symptoms did not transmit virus vertically to their offspring (Melville and Griffiths, 1999). However, whether transmission of ISAV can occur from ISA-diseased broodstock has not been clarified.
As ISAV replicates in sea trout, it has been discussed whether this species could be a marine reservoir of the virus. In Norway, sea trout are abundant in fjords and coastal areas, i.e. in the vicinity of fish farms, while the feeding areas of wild Atlantic salmon are distant from the coast in the North Atlantic. Infectious salmon anaemia virus seems to persist in infected fish for at least 7 months (Nylund and Jakobsen, 1995). The possibility therefore exists that outbreaks of ISA in farmed Atlantic salmon may cause a persistent ISAV infection in sea trout. The migratory behavior of sea trout may explain the appearance of disease in fish farms located far from ISA-affected farms.
Impact SummaryTop of page
|Fisheries / aquaculture||Negative|
Impact: EconomicTop of page
Although the loss of fish due to mortality may be significant, the most severe economic impact of the disease on the fish farming industry may be due to the specific restrictions described elsewhere. [See Husbandry Methods and Good Practice in the Disease Treatment, Prevention and Control section].
Impact: EnvironmentalTop of page
It is not known whether ISAV has any impact on the wild population of salmonids or non-salmonids in the vicinity of ISA-affected farms.
Zoonoses and Food SafetyTop of page
This species is not a zoonosis.
ReferencesTop of page
Aspehaug V; Falk K; Krossoy B; Thevarajan J; Sanders L; Moore L; Endresen C; Biering E, 2004. Infectious salmon anemia virus (ISAV) genomic segment 3 encodes the viral nucleoprotein (NP), an RNA-binding protein with two monopartite nuclear localization signals (NLS). Virus Research, 106:51-60.
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