Vertical transmission of infectious disease in cattle (Proceedings)
The potential for several economically important infectious diseases of cattle to be vertically transmitted from dam to offspring is of understandable concern to veterinarians and producers alike.
The potential for several economically important infectious diseases of cattle to be vertically transmitted from dam to offspring is of understandable concern to veterinarians and producers alike. A proportion of the research into several of the major contagious, infectious diseases of cattle such as bovine leukosis virus (BLV), bovine viral diarrhea virus BVDV), and Johne's disease has been oriented towards elucidating the risks that maternal infection represents for true transplacental spread in utero to the fetus, or the immediate post-natal spread of disease from dam to calf. Included within a more complete list of infectious agents for which there has been avid discussion of the relative risk of vertical transmission are bovine viral diarrhea virus (BVDV), bovine leukosis virus (BLV), Mycobacterium paratuberculosis, blue tongue virus (BTV), Neospora caninum and bovine spongiform encephalopathy. Veterinarians and producers that deal with predominantly grade cattle of lesser individual value are necessarily concerned about the production and economic implications of vertically acquired infectious agents, whereas those who work with individually valuable animals, particularly those involved in assisted reproductive technologies such as conventional in vivo embryo transfer, oocyte recovery and in vitro fertilization have greater concerns about product quality and the pure infectious disease status of the dam and progeny produced. For several of the diseases named above international export and import concerns are prominent.This presentation will focus on the current knowledge regarding vertical transmission of several of these key diseases and the implications for veterinarians working with all types of cattle.
Bovine leukosis virus
The ability of BLV to effect both horizontal and vertical transmission has long been recognized. The proportionate importance of vertical transmission is far less than horizontal, with the majority of infectious spread being via transfer of BLV infected lymphocytes in blood, colostrum and milk. Iatrogenic transmission during cattle handling, processing and routine husbandry is a frequent means of spread that is commonly targeted by control programs. Serologic surveys within the US show wide variation in state by state infection levels but a consistent finding amongst studies is that dairy breeds have a higher seroprevalence than do beef breeds1. The possibility of transplacental infection from a BLV positive cow to her calf in utero has long since been verified but there is little recent data that adds to the literature from the 1980s and 1990s. Epidemiologic studies examining in utero spread in BLV positive dams via pre-colostral blood testing of neonates have demonstrated vertical transmission rates that vary from 0.5% to 18%1. Maternal lymphocytosis (>12,000/µL) and a high herd seroprevalence appear to be factors that may increase the vertical transmission rates in these epidemiologic studies1,2. The dam's age, parity and whether or not maternal infection takes place during pregnancy are factors that do not appear to increase the likelihood of in utero transmission1. Studies on commercial dairies in the US would suggest that 4% is a reasonable estimate for the proportion of progeny that will be born infected from seropositive dams. Semen from BLV infected bulls is not considered infective, unless there is significant leucopsermia and infected lymphocytes are transferred. Similarly, ova and embryos from BLV positive donors are not considered sources of infection for recipient animals.
Bovine viral diarhhea virus
Of all bovine infectious diseases the pathogenetic significance of vertical transmission is perhaps best elucidated for BVDV. The relevance of transplacental infection in early gestation (prior to 120 days) as a means of viral persistence within cattle populations is manifest. Infection with non-cytopathic strains of BVDV (ncp BVDV) before fetal immunocompetence can result in a persistently infected calf if the pregnancy goes to term. These PI calves represent a major reservoir of infective virus on farms and propagate the disease within cattle populations. The mechanisms by which ncp BVDV establishes the PI status are complex and appear to be associated with avoidance of an appropriate host innate immune response to viral infection within the fetus, despite normal concurrent anti-viral responses in the dam3. Interference with normal type 1 interferon responses appears to be important in viral persistence and establishing the PI status4. BVDV infected, cryopreserved, or fresh semen have long been documented as potential means of horizontal transmission of infection with subsequent consequences for in utero transmission before fetal immunocompetence occurs; however current USA and international requirements for infectious disease screening of sires should reduce this risk to near zero if appropriately followed. Natural service or herd bulls should therefore be screened in a comparable way for biosecurity reasons. The risks for vertical transmission of BVDV via traditional in vivo or in vitro embryo transfer technologies appear to be very low, but not zero5,6. Typical embryo washing and trypsin treatment appear to remove all but a few very high affinity strains of BVDV but under certain experimental conditions virus may still be retained on in vivo produced embryos7. Whether or not this is ever sufficient for infectivity is uncertain. Consequently, concurrent vaccinal protection of donors and recipients is suggested. The resistance of the zona pellucida to virus infection may well serve to protect IVF embryos from internal infection but there is evidence that this technique can result in greater embryo associated virus being introduced via the surface of the zona pellucida than is the case with conventional in vivo transfer7. Subsequent uterine tubule infection could result but the pathogenetic significance of this in natural disease transmission is uncertain at this time for IVF embryos. Embryo donor, recipient and semen donor screening are of obvious critical importance in preventing spread of BVDV by this means, as is the quality control of all sera and bovine fluids used in the process. It is probable that similar concerns exist for embryos derived via somatic cell nuclear transfer as do for IVF embryos7,8.
Bovine spongiform encephalopathy
The etiologic and pathologic similarities between BSE and scrapie alongside the documented cases of BSE in progeny of affected dams and beyond the temporal institution of regulations banning animal by-product feeding of cattle has led to considerable interest in the possibility of vertical transmission of BSE in cattle. However, at this time there is no definitive proof that this occurs. Similarly, embryo transfer has not been proven to be a means of BSE transmission when infected donors or bulls were used9,10,11.
Blue tongue virus
Interest in vertical transmission of BTV is not so much driven by the clinical severity or relevance of the infection in cattle as it is by the reportable nature of the disease and its major importance in the international trade of animals and animal products. This is particularly relevant for producers who deal with the European and Asian export markets. Up until very recently experimental attempts to demonstrate transplacental infections of calves with wild type virus had been unsuccessful in pregnant cattle, although there are numerous studies that document successful transplacental transmission with cell attenuated BTV strains12. During early gestation the most likely reproductive consequences of fetal infection are fetal death and resorption with impaired fertility in the dam. Some aborted bovine fetuses following BTV exposure will demonstrate similar teratogenic defects involving the CNS and ocular system that can also be seen with BVDV infection. However later term experimental infection has been associated with the birth of weak, low birth weight calves that may also be viremic. Clinical experience in Europe during recent outbreaks of the disease have heavily suggested that transplacental infection might be a significant means by which the virus persists in cattle populations but it was not until very recently that the possibility that wild type BTV could be transmitted transplacentally following oral inoculation of a pregnant dam was verified12,13,14. Interestingly that particular study utilizing BTV type 8 (a strain not yet identified in North America) was performed using cattle that were late pregnant, well beyond the time in gestation when fetal immunocompetence develops12. Although BTV can be transmitted in semen and this can represent a potential means of horizontal infection, it does not appear that embryo transfer is a significant mode of transmission.
Transplacental infection with Neospora caninum is a major means of spread for the organism. Recently there has been an effort to adopt the terms endogenous and exogenous transplacental infection so as to distinguish between vertical transmission that arises due to a novel, acute infection of a pregnant dam (exogenous) versus that occurring in a pre-existent, chronically infected dam. (endogenous)15,16. Recent studies have demonstrated that oocytes and early embryos are not exposed to the organism in the uterus of seropositive dams such that embryo transfer can be an authentic technique for eliminating vertical transmission16. Current embryo transfer techniques are therefore an effective way of deriving replacement stock that are seronegative regardless of the status of the dam.
The fact that the majority of cattle become infected with this agent in the immediate neonatal period can often make the issue of whether or not true, in utero, vertical transmission occurs moot, particularly in grade cattle. The feco-oral route is the predominant means of spread and the mode of transmission that producers should be focused on for control purposes. However it is not usual for clients and veterinarians involved in the field of embryo transfer to seek information as to whether or not a donor or recipient could potentially transmit the disease in utero to a valuable calf. This question is most commonly asked from the perspective of the older, seropositive embryo donor, or in the context of screening recipients prior to their use. The individually valuable mature cow with clinical Johne's disease from whom a client is trying to acquire "one last calf" is another scenario in which we may be asked to give an opinion as to the likelihood of vertical transmission. The literature provides some guidance but is by no means declarative at this point in time. Many of the published studies on in utero transmission of M.paratuberculosis are epidemiologic in nature and can be best summarized by the sparingly useful comment that the incidence of calves infected in utero on any farm increases as the ratio of clinical cases to sub-clinical ones goes up. However, epidemiologic studies suggest that the estimated incidence of true vertical transmission in herds with a within herd prevalence of 5% is about 0.44-1.2 infected calves per 100 cows compared to 3.5-9.3 calves per 100 cows when the herd prevalence rises to 40%17. The risk of in utero transmission markedly increases in such studies when one considers dams showing clinical signs compared to those as yet only subclinically infected. Estimates place approximately 9% (6-14%, 95% CI) of calves from subclinically infected dams as being likely to be infected in utero versus approximately 39% (20-60%, 95% CI) of those born to dams with clinical signs17. Studies examining the safety of embryo transfer or IVF techniques suggest that the zona pellucida is an effective barrier to the organism and that neither technique represents a risk for transmission of the infection from donor to fetus or donor to recipient, provided that the sequential washing procedures suggested by the IETS are observed18.
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