Viral hemorrhagic septicemia

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Virael hemorrhagic septicemia
Internal hemorrhages associated with VHS

Viral hemorrhagic septicemia (VHS) is a viral disease of fishes caused by a rhabdovirus designated as the viral hemorrhagic septicemia virus[1].

The virus infection occurs in salmonids and certain other fishes of any age and may result in significant cumulative mortality. Fish that survive may become carriers. Viral hemorrhagic septicemia has been reported under various names, of which "Egtved disease" and "Infektiose Nierenschwellung und Leberdegeneration" are the best known. Several serotypes of the virus (also known as "Egtved virus") are currently recognized[2].


At least three VHS virus serotypes (designated F1, F2, 23.75) can be distinguished by infectivity neutralization assays[3]. The VHS virus can be recovered from homogenates of internal organs, sex products, or urine. Concentrations of virus are higher in the anterior kidney and spleen than in liver, heart, or muscle. Mixed virus infections have been reported in which VHS virus was isolated from fish concurrently infected with infectious pancreatic necrosis virus. The isolation of VHS virus in cell culture is the standard for diagnosis.


Viral hemorrhagic septicemia is enzootic in most countries of continental Eastern and Western Europe, and the virus has been isolated in the Puget Sound area of Washington in the United States. No outbreaks of VHS or isolations of VHS virus have been reported elsewhere.

In Europe, epizootics of VHS occur primarily in rainbow trout, Oncorhynchus mykiss; brown trout, Salmo trutta; and to a lesser extent in northern pike, Esox lucius[4]. Natural infections have also occurred in grayling, Thymallus thymallus, and whitefish Coregonus sp[5]. Outbreaks of VHS have been suspected in pollan, Coregonus lavaretus, and lake trout, Salvelinus namaycush. In the United States, natural infections have been diagnosed in chinook salmon, O. tshawytscha; coho salmon, O. kisutch; and steelhead (searun rainbow trout).

Clinical signs

A variety of clinical signs and histopathologic changes may be apparent in fish infected with VHS virus. Some fish show frank clinical manifestations of disease, whereas others look normal. Historically, clinical and pathologic signs of VHS have been catalogued into acute, chronic, and latent forms. Such descriptions represent degrees of severity rather than progressive stages of the disease.

Acute signs are typically accompanied by a rapid onset of heavy mortality. Fish are lethargic, dark in color, exophthalmic, and anemic. Hemorrhages are evident in the eyes, skin, and gills and at the bases of the fins. Internally, punctiform hemorrhages are evident in periocular tissues, skeletal muscle, and viscera; the liver appears mottled and hyperemic and the kidneys are red and thin. In chronically infected fish, significant cumulative mortality occurs, but is protracted. Fish are lethargic, dark in color, exophthalmic, and severely anemic, but not grossly hemorrhagic. The abdomen is markedly distended due to edema of the liver, kidneys, and spleen. The liver appears pale and petechiated, and the kidneys are ashen. In a latent infection, mortality is low, and the fish seem nearly normal, but may be hyperactive. Inapparent virus carriers show no clinical signs of VHS[6].


Diagnosis is primarily based on presenting clinical signs and histopathological changes.

Histopathologic changes are generally confined to the liver, kidneys, spleen, and skeletal muscle[7]. In acutely affected fish, the liver sinusoids are engorged with blood, and hepatocytes show focal to extensive necrobiotic changes-cytoplasmic vacuoles, pyknosis, karyolysis, Iymphocytic invasion, and occasionally intracytoplasmic and intranuclear inclusions. Similar changes occur in the spleen and in the hematopoietic and renal elements of the kidneys. In skeletal muscle, erythrocytes sometimes accumulate in muscle bundles and fibers, but little tissue damage occurs. In chronically infected fish, liver sinusoids remain enlarged and contain coagulated plasma, and kidney and splenic hematopoietic tissues and mononuclear lymphoid cells are hyperplastic. No remarkable histopathologic changes have been reported in inapparent virus carriers.

In captive fish, culture and environmental stress seemingly increase susceptibility and recurrence of infection (Ghittino 1965; de Kinkelin 1983). In feral fish, inapparent infection is more common than disease[8].


Prevention of contact between the virus and the host is the most effective method for controlling VHS. A systematic program of hatchery disinfection, combined with restocking with specificpathogenfree fish and eggs, has been used successfully[9]. Eggs used for restocking are decontaminated by iodophor treatment. The water supply should ideally be controlled and virusfree, although ultraviolet irradiation has been used to inactivate VHS virus in the water supply (Maisse et al. 1980). Conditions that promote physiological stress should be alleviated. Although VHS rarely occurs above 15°C, disease control by temperature manipulation has not been described. Selective breeding to increase host resistance to VHS has not been successful.

The potential for vaccinating fish against VHS has been demonstrated, and several avirulent VHS virus vaccines are under development. One vaccine candidate, a VHS virus variant of low pathogenicity (F25), was selected by serial passage in EPC cells at progressively increasing temperature. This F25 variant replicates at 25°C, but the wildtype virus does not[10]. A second vaccine candidate, a low-pathogenicity virus strain (Reva), was selected by serial passage in RTG2 cells. Although both the F25 and the Reva strains induced a protective response, they also retained residual pathogenicity. The mechanism of the protective response is unclear. Some mechanism occurring within 48h after immunization, such as interferon stimulation, might be responsible for early protection, whereas the antibody response occurs later. Fry can be protected by injection of interferon. Although the protective effects of avirulent vaccines have been demonstrated in the laboratory, their efficacy under production conditions has not been proven, and their value for controlling VHS in healthy fish populations has been questioned[11].


  1. Office International des Epizooties. (1963) Resolutions Bull Off Int Epizoot 59:291295
  2. Jensen, MH (1965) Research on the virus of Egtved disease. Ann NY Acad Sci 126:422426
  3. de Kinkelin, P., and J. Castric. (1982) An experimental study of the susceptibility of Atlantic salmon fry, Salmo salar L., to viral haemorrhagic septicaemia. J. Fish Dis. 5:5765
  4. Jorgensen, PEV (1980) Egtved virus: the susceptibility of brown trout and rainbow trout to eight virus isolates and the significance of the findings for the VHS control. Pages 37 in W. Ahne, ed. Fish diseases. Third COPRAQSession. SpringerVerlag, Berlin, Heidelberg, New York
  5. Wizigmann, G., C. Baath, and R. Hoffmann. (1980) Isolation of viral hemorrhagic septicemia virus from fry of rainbow trout, pike, and grayling. Zentralbl Veterinaermed Reihe B 27:7981
  6. Yasutake, W. T. (1970) Comparative histopathology of epizootic salmonid virus diseases. Pages 341350 in S. F. Snieszko, ed. A symposium on diseases of fishes and shellfishes. Am Fish Soc Spec Publ 5
  7. Wolf, K. (1988) Fish viruses and fish viral diseases. Cornell University Press, Ithaca, N.Y. 476 pp
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  9. Kehlet, N. P. (1973) A summary of the rules, methods and results of the Danish campaign against infectious disease of freshwater fish. EIFAC [Eur Inland Fish Advis Comm] Tech Pap 17(2):3738
  10. Bernard, J., M. BearzottiLe Berre, and P. de Kinkelin. (1985) Viral haemorrhagic septicaemia in rainbow trout: attempt to relate interferon production, antibody synthesis and structure of the virus with the mechanism of virulence. Ann Inst Pasteur/Virol 136:1326
  11. Enzmann, P. J. (1983) Considerations on the effectiveness of VHSvaccination. Bull Eur Assoc Fish Pathol 5:5455