Ashok Kumar*, Ajay Kumar Yadav, Vishal Rai, Mukesh Bhatt and Laxmi Upadhyay
ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243122
*Corresponding author; vetashok5@gmail.com
Introduction
Abortion in dairy cattle is commonly defined as a loss of the fetus between the age of 42 days and approximately 260 days. Pregnancies lost before 42 days are usually referred to as early embryonic deaths, whereas a calf that is born dead between 260 days and full term is defined a stillbirth. A low rate of abortions is usually observed on farms and 5% to 10% abortions per year are often considered “normal.” Abortion among dairy cows represents a major economic burden to the cattle industry. In large dairy herds, it has been suggested that an abortion rate of 5% to 10% is to be expected, and this estimate is used as a parameter (endemic abortion rate); greater percentages are termed abortion storms. Each abortion is estimated to cost the producer $500 to $900 – depending on such factors as the current value of replacement stock, feed and milk prices, and the stage of gestation when the abortion occurs. The diagnosis of abortions often presents a challenge to the herd owner and the herd veterinarian. For this reason, prompt and thorough action is required when abortions do occur. Well kept records will often be of benefit during the investigation of abortion problems.
- Bovine Viral Diarrhea virus (BVDV)
In several surveys, BVD was the most commonly diagnosed virus in bovine abortion cases. The pathology of BVD in the developing fetus is complex. BVD can cause a whole range of disease syndromes in cows. When the virus circulates in the cow, it is able to reach the growing fetus through the placenta. Infection before insemination or during the first 40 days of pregnancy results in infertility or embryonic death. Infection between 40 and 125 days of pregnancy results in birth of persistently infected calves if the fetus survives. Fetal infection during the period of organogenesis (100–150 days) may result in congenital malformations of the CNS (cerebellar hypoplasia, hydrancephaly, hydrocephalus, microencephaly, and spinal cord hypoplasia). Congenital ocular defects have also been seen (cataracts, optic neuritis, retinal degeneration, microphthalmia).After 125 days of gestation, BVD may cause abortion, or the fetal immune response may clear the virus. However, if the calf is exposed to the BVD virus between 40 and125 days of gestation, and if it does not die, it may be born as a “persistently infected” calf. During the second 3 months of gestation, an infection may result in an abortion, or a calf which will be born with birth defects. Generally if a calf is exposed in the uterus during the last trimester, the virus will have no effect on the calf, except that it will be born with antibodies to BVD in its blood. Occasionally a late-gestation abortion may result from a BVD virus infection. While immunity in the cow (by exposure or vaccination) should help to protect the developing fetus, the protection offered is not 100% since there are different strains of BVD virus and only a few virus particles need to get to the fetus to cause an infection.
| Fig.1: Transmission and pathogenesis of BVDV |
Diagnosis
Diagnosis is by identification of BVD virus by isolation, immunologic staining, PCR, or detection of precolostral antibodies in aborted calves. The virus is present in a wide variety of tissues, but the spleen is the tissue of choice.
Prevention
The use of an effective BVD vaccine should be a routine part of a herd disease prevention program.
- Infectious Bovine Rhinotracheitis virus (IBR, BHV-1)
Infectious bovine rhinotracheitis (IBR) is a major cause of viral abortion in the world, with abortion rates of 5%–60% in nonvaccinated herds. The virus is widespread, causes latent infections, and can recrudesce; therefore, any cow with a positive IBR titer is a possible carrier. BHV-1 is a serious contagious herpes virus disease of cattle that can cause a variety of different disease syndromes, the most common of which is respiratory disease (pneumonia, “red nose”). Abortions most commonly occur from 4 months to term, and may occur weeks after the disease has gone through the herd. Autolysis is consistently present. Occasionally, there are small foci of necrosis in the liver, but in a large majority of cases there are no gross lesions in the placenta or fetus. Microscopically, small foci of necrosis with minimal inflammation are consistently present in the liver. Necrotizing vasculitis is common in the placenta.
| Fig.2: Aborted fetus due to BHV-1 Infection |
Diagnosis
Diagnosis can be made by immunologic staining of the kidney, lung, liver, placenta, and adrenal glands. IBR virus can be isolated from ~50% of infected fetuses (most successfully from the placenta).
Prevention
The use of effective IBR vaccines should be a routine part of a herd disease prevention program; intranasal, modified-live virus, and killed vaccines are available.
- Bluetongue
Bluetongue was first described in the Cape Colony of southern Africa, soon after the introduction of European sheep to the region. Epizootics of bluetongue subsequently were reported in the middle of the 20th century in the United States, countries of the Mediterranean basin, the Middle East, and Asia including India. Bluetongue disease is caused by bluetongue virus (BTV) an Orbivirus with 27 serotypes and is transmitted by biting midges of the genus Culicoides. the majority of field strains of bluetongue virus rarely cross the placenta, where as some laboratory-adapted viruses (such as liveattenuated vaccine strains, especially those propagated in embryonated eggs) readily cross the placenta to cause fetal infections and either fetal death or developmental anomalies (congenital hydranencephaly or porencephaly). Similarly, the few previously documented instances of fetal infection and virus-induced cerebral malformations in cattle occurred in areas where live-attenuated vaccines have been used, suggesting that natural circulation of these vaccine viruses. After introduction of an attenuated, live virus vaccine in the 1950s, abortion, mummification, stillbirth, and the birth of live offspring with CNS malformations occurred in cattle and sheep. Attenuation of bluetongue virus can increase its ability to cross the placenta. In 2006, serotype 8 bluetongue virus (Toggenberg virus) appeared, spread, and became endemic across northwestern Europe where bluetongue was previously unknown and this virus is pathogenic to cattle.
Diagnosis
The clinical presentation and lesions of bluetongue are characteristic, as is the seasonal nature of the disease in temperate regions. Virus isolation is carried outin embryonated eggs (Intravenous) or in cell cultures (BHK-21 or Vero cells), but both systems can be quite insensitive. RT-PCR assays, especially quantitative PCR assays, now are the standard for virus detection;however, ruminants remain positive by this assay months after infectious virus has been cleared from the blood.Serologic techniques, most notably competitive enzymeimmunoassays, based on the detection of antibodies to the VP7 group antigen, are used extensively for regulatory purposes involvingthe international livestock trade.
Prevention
Control of bluetongue virus infection is almost exclusively by vaccination, as elimination of vector insects is generally impractical. Inactivated and live-attenuated bluetongue virus vaccines are available in different areas of the world. Live-attenuated vaccines to most viral serotypes were developed long ago in South Africa and the United States. These vaccines generally provide strong, serotype specific protective immunity after a single inoculation, and they prevent clinical disease; however, attenuated virus vaccines also have inherent potential disadvantages: (1) some live-attenuated vaccines, especially those propagated in embryonated eggs, were associated with reproductive losses, including fetal death and congenital cerebral abnormalities, when administered to pregnant sheep; (2) under-attenuated vaccine viruses can induce clinical reactions in vaccinated animals.
Inactivated vaccines are safe, but they are limited to a few serotypes and
revaccinations are necessary. In India inactivated pentavalent vaccine including five serotypes (1, 2,10, 18, and 23) is now currently used. An extensive variety of recombinant bluetongue virus vaccines recently have been developed, but they are not yet commercially available.
- RIFT VALLEY FEVER VIRUS
RVF virus was discovered in the late 1980s that the virus is transmitted transovarially among floodwater Aedes spp. mosquitoes; the virus survives for very long periods in mosquito eggs laid at the edges of usually dry depressions, called “dambos,”. Large number of mosquitoes emerges after heavy rains or when improper irrigation techniques are used; they feed indiscriminately on viremic sheep and cattle (and humans). After entry by mosquito bite, percutaneous injury, or through the oropharynx via aerosols, there is an incubation period of 3072 hours, during which virus invades the parenchyma of the liver and lymphoreticular organs. Extensive hepatocellular necrosis is common in terminally affected sheep. The spleen is enlarged and there are gastrointestinal and subserosal hemorrhages. However, a sudden onset of abortions among sheep, goats, cattle or camels over a wide area is probably the most significant sign. There will also probably be sudden deaths and disease with many fatalities in all species, especially in the early post-natal period. Abortion is perhaps the most common consequence and this may occur during the acute phase of the disease or up to six to eight weeks later. Some deaths may occur. A persistent ill thrift may follow such mild infections, which is usually associated with moderate to severe jaundice and liver damage. Photosensitization is a common sequel to RVF virus infections.
Diagnosis
Because of its broad geographic distribution and its explosive potential for invading new areas where livestock husbandry is extensive, the laboratory confirmation of the presence of Rift Valley fever virus is treated as a diagnostic emergency. Rapid diagnosis is achieved using RT-PCR assays and can be confirmed by virus isolation by intracerebral inoculation of mice or in cell culture. The virus replicates in a variety of cell cultures such as Vero E6 and BHK-21 cells, and the virus is rapidly cytopathic and causes plaques.Nucleic acid sequencing and immunologic methods are used to establish the identity of isolates. Serologic diagnosis is by immunoglobulin (IgM) capture enzyme immunoassay on single acute sera, or by enzyme immunoassays, neutralization, or hemagglutination-inhibition assays on paired sera from surviving animals. Veterinarians and laboratory workers are at substantial risk during postmortem examination of animals or processing diagnostic materials in the laboratory.
Prevention
Control is based primarily on livestock vaccination, but vector control (via use of mosquito larvicides and insecticides) is also used during outbreaks. In addition, environmental management can be a useful control strategy, including assessment of the risk of creating new larval habitats (water impoundments, artificial dambos) in enzootic areas. Attenuated-virus Rift Valley fever vaccines produced in mouse brain and in embryonated eggs is effective and inexpensive for use in sheep and cattle, but they cause abortions in pregnant animals. Inactivated-virus vaccines produced in cell cultures avoid the problem of abortion, but are more expensive to produce.
- Akabane virus
Akabane virus is best known for its teratogenic effects in ruminants, with seasonal epizootics of reproductive loss (embryonic/fetal mortality, abortion) and congenitalarthrogryposis and hydranencephaly. Infection of pregnant cattle or sheep can lead to one of two outcomes: death of the fetus and abortion, or birth, sometimes premature, of progeny with congenital defects. Affected fetuses characteristically have extensive cavitary defects of the central nervous system (hydranencephaly) and severe musculoskeletal abnormalities (arthrogryposis), thus abortion or birth is often accompanied by dystocia. Fetuses born with hydranencephaly usually are unable to stand after birth; those less severely affected may manifest marked incoordination and a variety of other neurologic deficits (“dummy calves”). Fetal infection results in both encephalomyelitis and polymyositis, and virus replication within the developing central nervous system leads to destruction of the developing brain and subsequent hydranencephaly.
Diagnosis
In enzootic areas, diagnosis of Akabane virus infection may be suggested by clinical, pathologic, and epidemiologic observations (seasonal occurrence), but most often by gross pathologic examination. Diagnosis is confirmed by the detection of specific antibodies in serum or fluids (pleural, pericardial) collected from aborted fetuses or from newborn calves, kids, or lambs before ingestion of colostrum. However, virus can be recovered from the placenta, brain or muscle of aborted fetuses, or from tissue samples taken from fetuses removed by cesarean section before normal parturition or after slaughter of the dam. Virus isolation is carried out in cell cultures or by intracerebral inoculation of suckling mice.
Prevention
Both inactivated and live-attenuated vaccines are available for protective immunization of livestock against Akabane virus infection.
- Foot and mouth disease virus
Foot-and-mouth disease virus is the type species of the genus Aphthovirus, family picornaviridae. Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. Foot-and-mouth disease remains a major global animal health problem with regular occurrence of disease epidemics, but its geographic distribution has diminished in recent years as control and elimination programs have been established in increasingly more countries. Seven serotypes of foot-and-mouth disease virus have been identified by cross-protection and serologic tests; they are designated O, A, C, SAT 1, SAT 2, SAT 3, and Asia 1. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD affected and asymptomatic cows. The virus cannot cross the placenta but abortions may occur in cattle because of high fever rather than infection of the fetus itself.
Diagnosis
A range of diagnostic tests is available for the differentiation of the vesicular diseases of livestock, including foot-and-mouth disease. Rapid differentiation of the agents causing vesicular disease is now available using multiplex RT-PCR assays, and RT-PCR tests can also be used to identify specific serotypes of foot-and-mouth disease virus. A capture immunoassay (sandwich ELISA) is also available whereby a diagnosis can be made within a few hours. This test can also be used to identify which of the seven types of foot-and-mouth disease virus is the cause of the disease. Competitive and indirect ELISAs are also available for specific antibody determinations, and ELISA tests that detect antibodies to the nonstructural proteins of foot-and-mouth disease virus have been developed in an attempt to distinguish animals vaccinated with killed vaccines from those naturally infected with the virus (DIVA). Virus neutralization assays have been a mainstay in the serological diagnosis of foot-and-mouth disease virus, but testing is complicated by the plurality of viral serotypes. Cell cultures are used to isolate virus from clinical specimens in order to confirm the identity of the agent and to obtain virus isolates for genetic and antigenic analysis. Primary cultures of bovine, porcine, or ovine kidney are more sensitive than established cell lines such as BHK-21 or IB-RS-2 cells. Cell cultures are generally used to isolate the virus from tissues, blood, milk, and esophageal or pharyngeal fluids.
Prevention
The immunity following natural infection has stimulated attempts at developing an effective vaccine. As seen with natural infections, a vaccine strategy based on a single serotype will not work to control infections by the other serotypes. Even within a serotype, antigenic variation may make a vaccine less effective than is necessary to prevent infection. In India BEI inactivated trivalent vaccine containing serotype O, A and Asia-1 with mineral oil adjuvanted is used. There is continued interest in the United States in particular to develop recombinant adenovirus-vectored subunit vaccines in order to eliminate the biohazard of using any live virus in vaccine production. Creating check post or regulating animal movements from infected to uninfected area can reduce the occurrence of disease.
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