Skip to main content

An Unusual Congenital Malformation in a Calf with Serological Evidence of Foetal Bovine Viral Diarrhoea Virus Infection

Bovine viral diarrhoea (BVD) virus is maintained in the environment by persistently infected animals [8]. The BVD virus in an immunocompetent pregnant animal is capable of crossing the placental barrier and invading the foetus [12, 9]. The principal determinant of foetal response to infection is the age of the foetus at the time of infection [1], and the differing ability of different strains of BVD virus to produce congenital defects [11, 19]. Breed variation and immune status of the host may also be important factors in determining the foetal effect.

The possible outcomes of foetal infection include foetal resorption, abortion, mummification, congenital malformations, birth of weak and undersized calves, birth of calves persistently infected with BVD virus, and birth of normal calves. Foetopathology caused by BVD virus infection during the first trimester has been well documented [13, 7, 20, 4, 3, 9, 21, 2, 17, 18]. The following congenital defects have been described: cerebellar hypoplasia, hydrocephalus, hydranencephaly, with or without cranial deformation, dysmyelination of the spinal cord, lenticular cataracts, microphthalmos, chorioretinopathy, alopecia, brachygnathia, intrauterine growth retardation and thymus hypoplasia.

This report describes an unusual congenital malformation in a calf, where there was serological evidence of foetal BVD virus infection. The male calf was born to a 3.5-year-old dairy cow after a prolonged gestation (294 days), and 15 min after the calving the animal died. The first female calf born to this cow, one year previously, was normal. The well managed dairy cattle herd (Israeli-Holstein breed), comprising 40 lactating cows, was kept under a zero-grazing management system in open barns, all the year round, with a rolling herd milk production average of 9,000 kg. The herd had not been routinely vaccinated against BVD infection. This unusual malformation was one-off occurrence, and there were no other indications of BVD virus – associated in this herd. Serological survey by ELISA test showed a prevalence of 89% for BVD virus in this particular herd.

Pre-colostral serum from heart blood of the newborn calf and a blood sample from the dam were collected for detection of neutralizing antibodies and for virus isolation.

Cell culture

Kidneys and lungs from bovine foetuses, obtained from a local abattoir, formed the source for the cell cultures. Preparation of the cell suspension was performed according to standard procedures [15].

Screening for adventitious BVD virus

Five millilitres of the final cell suspension were cultured separately, passaged three times at weekly intervals, and each passage was tested for the presence of BVD virus by an indirect immunofluorescence (IF) assay (Hyclone Laboratories, Inc., UT, USA). Briefly, at each passaging, a drop of the cell suspension (approximately 10000 cells/drop) was dried on a glass slide, fixed in 100% acetone for 10 min and allowed to dry. The spotted sample was incubated with diluted bovine anti-BVD virus antiserum in a humid chamber for 30 min at 37°C, washed 3 times with carbonate/bicarbonate buffer, then incubated with diluted goat anti-bovine IgG/FITC in a dark humid chamber for 30 min at 37°C. After 3 additional washes with carbonate/bicarbonate buffer, a mounting buffer of 50% glycerol was applied and the slide was observed under epifluorescent lighting (Nikon Optiphot, Osram XBO 100 W OFR mercury lamp, FITC filter). Positive and negative controls were included in each test.

Sera were heated at 56°C for 30 min and examined in a neutralization assay in microtitre plates, using a 1-h incubation at 37°C with cytopathogenic BVD virus isolate (100 TCID50 per well) and serial twofold serum dilutions. If inhibition of the cytopathic effect was observed at any dilution, the serum was considered to be negative for BVD virus-neutralizing antibodies.

The following congenital malformations were observed: The 2 orbits had merged and formed a single cavity containing one eye (Figs 1 &2); generalized alopecia was present, except for the eye, mouth, ears and tail end (Figs 1 &2); distorted upper jaw and nose, palate cleft or almost totally absent. There was a long median cutaneous protuberance (8 cm long) (Fig. 2) above the single eye. The cerebral hemispheres were fused, with hydrocephalus in the lateral ventricles. The optic nerves were also fused. The pituitary gland was absent, apparently causing an oversize foetus with a prolonged gestation. Serum obtained from the calf had a virus neutralization titre of 1:8192 and that from the dam, 1:512. Blood from the dam was negative on virus isolation.

Figure 1

A single large eye in the middle of the face.

Figure 2

Generalized alopecia, except for the eye, mouth and ears. A long median cutaneous protuberance exists above the eye.

Malformation may arise when virus infection occurs during organogenesis and thus interferes with growth, differentiation and maturation of foetal tissue, whereas lesions may be the result of virus infections of already matured tissue [21]. Most reports of congenital anomalies of BVD infection have described one or 2 anomalies rather than multiple anomalies [2, 22, 17].

In the present case, BVD virus replicated apparently in a wide range of foetal tissues. The outcome depends upon the extent of the damage to actively dividing cells, the stage of foetal organogenesis, the development of foetal immune competence, and the ability of the foetus to mount an inflammatory response [10]. Alopecia has been related to maternal infection with BVD virus [14]. It seems that, in the present case, inflammatory or necrotizing lesions were severe enough to destroy the germinal epithelium or hair follicles during foetal development, which resulted in some degree of congenital abnormalities [7].

The high level of circulating anti-BVD antibodies was the result of an active immune response of the foetus to an intrauterine infection induced by a BVD virus. A similar observation was reported by [14] and by [16] and it indicates once again that the bovine foetuses are immunologically competent early in gestation. No foetal disease has been recognized to result from infection occuring after acquisition of full immune competence – around day 180 of gestation [5]. The time of infection of the foetus in the present case cannot be determined exactly, but the severe and multiple congenital anomalies observed in this newborn calf must have resulted from infection earlier in pregnancy – from about 42 to 125 days of gestation [6].

The presence of high pre-colostrum antibody titres in the serum of the anomalous calf is convincing evidence that a prenatal foetal BVD infection occurred. Although there is serological evidence that the calf had been infected with BVD virus, it cannot be ascertained whether the abnormality was due to the BVD virus infection.


  1. Baker JC: Bovine viral diarrhea virus: a review. J Am Vet Med Ass. 1987, 190: 1449-1458.

    CAS  Google Scholar 

  2. Binkhorst GJ, Fournee DLH, Wouda W, Straver PJ, Vos JH: Neurological disorders, virus persistence and hypomyelination in calves due to intrauterine infections with bovine virus diarrhoea virus : I. clinical symptoms and morphological lesions. Vet Quart. 1983, 5: 145-155.

    Article  CAS  Google Scholar 

  3. Brown TT, Bistner SI, Delahunter A, Scott FW, McEntee K: Pathogenic studies of infection of the bovine fetus with bovine viral diarrhea virus II. Ocular lesions Vet Pathol. 1975, 12: 394-404.

    CAS  PubMed  Google Scholar 

  4. Brown TT, De Lahunta A, Bistner SI, Scott FW, McEntee K: Pathogenic studies of infection of the bovine fetus with viral diarrhea virus I. Cerebral atrophy Vet Pathol. 1974, 11: 486-505.

    CAS  PubMed  Google Scholar 

  5. Brown TT, Schultz RD, Duncan JR, Bistner SI: Serologic response of the bovine fetus to Bovine Viral Diarrhea Virus. Inf Immun. 1979, 25: 93-97.

    Google Scholar 

  6. Brownlie J: Pathogenesis of mucosal disease and molecular aspects of bovine virus diarrhoea virus. Vet Microbiol. 1990, 23: 371-382. 10.1016/0378-1135(90)90169-V.

    Article  CAS  PubMed  Google Scholar 

  7. Casaro APE, Kendrick JW, Kennedy PC: Response of the bovine fetus to bovine viral diarrhea-mucosal disease virus. Am J Vet Res. 1971, 32: 1543-1562.

    CAS  PubMed  Google Scholar 

  8. Derget D, Loewen KG: Bovine viral diarrhoea virus. J Am Vet Med Ass. 1995, 36: 371-378.

    Google Scholar 

  9. Done JT, Terlecki S, Richardson C, Harkness JW, Sands JJ, Patterson DSP, Sweasey D, Shaw IG, Winkler CE, Duffell SJ: Bovine virus diarrhea mucosal disease virus: pathogenicity for the fetal calf following maternal infection. Vet Rec. 1980, 106: 473-479.

    Article  CAS  PubMed  Google Scholar 

  10. Duffell SJ, Harkness JW: Bovine virus diarrhoea-mucosal disease infection in cattle. Vet Rec. 1985, 117: 240-245.

    Article  CAS  PubMed  Google Scholar 

  11. Hafez SM, Liess B, Frey HR: Studies on the natural occurrence of neutralizing antibodies against six strains of bovine viral diarrhea virus in field sera of cattle. Zntbl Vet Med B. 1976, 23: 669-677.

    Article  CAS  Google Scholar 

  12. Kahrs RF: Effects of bovine viral diarrhea on the developing fetus. J Am Vet Med Ass. 1973, 163: 877-878.

    Google Scholar 

  13. Kahrs RF, Scott FW, DeLahunta A: Bovine Viral Diarrhea – Mucosal Diseases, abortion and congenital cerebellar hypoplasia in a dairy herd. J Am Vet Med Ass. 1970, 156: 851-857.

    CAS  Google Scholar 

  14. Kendrick JW: Bovine Viral Diarrhea-Mucosal Disease virus infection in pregnant cows. Am J Vet Res. 1971, 32: 533-544.

    CAS  PubMed  Google Scholar 

  15. Mahy BWJ, Kangro HO: Virology Methods Manual. 1996, Academic Press New York, 4-5.

    Google Scholar 

  16. Nettleton PE, Entrican G: Ruminant pestiviruses. Brit Vet J. 1995, 151: 615-642. 10.1016/S0007-1935(95)80145-6.

    Article  CAS  Google Scholar 

  17. Ohmann HB: An oculo-cerebellar syndrome caused by congenital bovine viral diarrhoea virus infection. Acta Vet Scand. 1984, 25: 36-49.

    Google Scholar 

  18. Roeder PL, Jeffrey M, Cranwell MP: Pestivirus fetopathology in cattle: Changing sequelae with fetal maturation. Vet Rec. 1986, 118: 44-48.

    Article  CAS  PubMed  Google Scholar 

  19. Sanders DE, Sanders JA, Sangenario J: Protection of newborn calves against bovine virus diarrhea by vaccinating their dams prior to parturition Agri-Practice. 1983, 4: 30-34.

    Google Scholar 

  20. Scott FW, Kahrs RF, De Lahunta A, Brown TT, McEntee K, Gillespie JH: Virus induced congenital anomalies of the bovine fetus. I. Cerebellar degeneration (hypoplasia), ocular lesions and fetal mummification following experimental infection with bovine viral diarrhea-mucosal disease virus. Cornell Vet. 1973, 63: 536-560.

    CAS  PubMed  Google Scholar 

  21. Van Oirschot JT: Congenital infections with nonarbo togaviruses. Vet Microbiol. 1983, 8: 321-361. 10.1016/0378-1135(83)90048-2.

    Article  CAS  PubMed  Google Scholar 

  22. Wilson TH, De Lahunta A, Confer L: Cerebellar degeneration in dairy calves: clinical, pathologic and serologic features of an epizootic caused by bovine viral diarrhea virus. J Am Vet Med Ass. 1983, 544-547.

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to I. Yeruham.

Additional information

Reprints may be obtained from: I. Yeruham, 4 Hagoren St., Gedera 70700, Israel. E-mail:, fax: 972-8-8699083.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yeruham, I., Michael, M. & Perl, S. An Unusual Congenital Malformation in a Calf with Serological Evidence of Foetal Bovine Viral Diarrhoea Virus Infection. Acta Vet Scand 42, 425 (2001).

Download citation


  • Bovine Viral Diarrhoea Virus
  • Serological Evidence
  • Bovine Viral Diarrhoea
  • Viral Diarrhoea Virus
  • Bovine Viral Diarrhoea Virus Infection