Porcine reproductive and respiratory syndrome virus (PRRSV) belonging to Arteriviridae family
Highly contagious disease of swine manifested by reproductive failure, and respiratory disease in young pigs. Worldwide occurrence; spread rapidly in swine-raising areas during last 15 years. Subclinical infection endemic in most swine herds; incidence of clinical disease lower but causes severe economic losses. Pigs become infected in nursery from older infected pigs; persistent infection for several months is common. Different antigenic strains with variable virulence. Natural infection or vaccination results in immunity, but viremia still common. Infection with virus may predispose to secondary infections of respiratory tract. Transmitted by direct contact, feces and discharges, importation of infected pigs into herds, aerosol infection and semen
Outbreaks of late gestation abortions, stillbirths, mummified fetuses, weak neonates, high rate of return to estrus. Problem may persist and recur for many months
Anorexia, fever, dyspnea, polypnea, coughing, unthriftiness, high mortality in young pigs and low in older pigs and breeding stock. Deaths occur in acute phase
Interstitial pneumonia with reduction in alveolar macrophages. Aborted and mummified fetuses, stillbirths, weak neonates with pulmonary lesions
Serological testing for viral antibody titers. Detection of virus in tissues and alveolar macrophages using immunofluorescent microscopy
Porcine reproductive and respiratory syndrome (PRRS) is associated with an RNA virus morphologically, structurally, and genomically similar to members of the genus arterivirus of the family Arteriviridae belonging to the Order Nidovirales. The virus was first isolated in Lelystad, The Netherlands in 1991 and called the Lelystad virus1,2 it is closely related to the equine virus arteritis virus. The Mystery swine disease of the USA was then shown to be a similar virus.3,4 These two strains are considered to be one virus but the European and North American strains are genetically5,6 and antigenically different.7 The US and European strains are only 55–70% identical at the nucleotide level.8 The current theory of its origin is that Lactic Dehydrogenase Virus of Mice infected wild boar in Central Europe and became adapted. It then went to North Carolina in the USA in wild boars.9 It is thought that the most likely date for a common isolate of the European strains is before 1981.10 The two species of PRRSv then developed separately on the two continents.11 Some evidence of this comes from a study of the number of nucleotides in ORF7 of the virus12 from the USA (372 nucleotides), EU (Lelystad types) had 387 nucleotides but the Lithuanian strains that were collected had 378 nucleotides. In tissue culture it was suggested that a recombination between US and European isolates was 10 000 times less likely to occur than between diverse European isolates.13
PRRS was first reported as a new disease in swine-raising areas in North America in 1986–1987,14 and in 1991 was recognized in, and spread rapidly across, western European countries.15 The disease was first recognized in Germany in 1990 and in The Netherlands in 1991, and occurs in Spain, France, Belgium, Denmark, Taiwan, and other countries. The rapid spread of the disease initially to the southwest of Europe and then to the north, paralleled the direction of the wind. Airborne spread was also suspected because even well-managed and isolated herds became infected.
Based on serological surveys, there is no evidence of infection in swine herds in Switzerland16 and Australia.17
The introduction of legislation in some countries to restrict the movement of pigs from affected farms slowed the spread of the disease, but airborne spread over distances of a few km continued to occur, particularly in areas of high pig population density.18
The terms ‘mystery pig disease’ and ‘blue-eared pig disease’ were used because the etiology was unknown and the skin of the ears of affected pigs commonly appeared blue. The disease affects pregnant gilts and sows, unweaned and recently weaned pigs, and growing–finishing pigs. Outbreaks of late-term abortions, high numbers of stillbirths and mummified or weak newborn piglets, and respiratory disease in young unweaned and weaned pigs are common. After ten or more years of acceptance and relief that the European virus was not so pathogenic as the North American virus it is now accepted in Europe that the recent evolution of the virus may now be causing as many problems as the USA virus always has done.
In endemic herds 30–70% of pigs may be seropositive to the virus and about 60% of herds have some seropositive pigs.19 While the seroprevalence may be high in herds in some regions, the incidence of clinical disease is lower and variable.20 Although the number of herds with the acute form of the disease has been decreasing, the infection is now endemic in many herds, characterized by increased mortality and suboptimal performance in nursery pigs, with active spreading of the virus mainly in nurseries. In endemically infected herds, subpopulations of infected animals may exist consisting of a low prevalence (< 10%) of seropositive animals in the breeding animals and a high prevalence (> 50%) of seropositive nursery piglets.21 The elimination of these susceptible subpopulations by exposing all members of a population to the virus is used as a control strategy in large herds in which there may be subpopulations of highly susceptible breeding females. The virus can persist in non-pregnant sows and be transmitted to naïve in contact sows.22 A PRRSv strain may persist in a herd for up to 3.5 years displaying as little as 2% variation in ORF5 during this period. In 78% of herds with multiple submissions genetically different strains were identified within 1 year of the original identification.23 Virulent PRRSv isolates exhibit longer viremias but of no more elevated levels but they induce higher death rates and cause more severe clinical signs in a respiratory disease model. More virulent strains grew to significantly higher levels in pigs than did cell culture adapted isolates. Pathogenic consequences and immunological responses of pigs to PRRSv are closely related to viral load in acute infections as reflected in viral titers in blood.24
The morbidity rate in young pigs may be up to 50% and mortality in nursery piglets can reach 25%. Death is usually associated with secondary bacterial infections such as Salmonella choleraesuis, Streptococcus suis, Actinobacillus pleuropneumoniae, Haemophilus parasuis. Major losses occur in reproductive failure but figures for the magnitude of reproductive losses during an outbreak are not readily available. In general, the reproductive performance of positive herds is significantly lower than negative herds.25
The severity and duration of outbreaks following infection are variable. Some herds may be devastated by high production losses, whereas other herds may have almost no losses. Differences in morbidity and mortality may be due to dose of virus at exposure, differences in host susceptibility, differences in strain virulence, environmental or housing differences, or the production practices in the herd.
Nursing piglets lacking maternal immunity, and young growing and finishing pigs and sows lacking acquired immunity from natural infection or vaccination are highly susceptible to infection and clinical disease. Severe disease appears to be more likely in large herds that have a large turnover of pigs, purchase replacements from other herds, and do not use a quarantine system. Introduction of the virus to previously virus-naive herds may cause severe economic losses. In the recent outbreaks in Denmark the study of 107 herds showed that a variety of hazards were identified including close neighboring herds, increasing herd size, purchase of semen from infected AI studs.26
The immune responses that are generated by PRRSV are not understood and the control of the disease by immune mechanisms is not understood. The core effect of the virus is to infect and cause abnormalities in the macrophages. Disturbed macrophages may fail to present antigen successfully. More importantly whatever cytokines are present in the pig or are induced by the PRRS in that particular host may determine the outcome). It was shown that PRRSv is slow to produce both neutralizing antibodies and a cell mediated immunity.27 It does produce an IFN response in PRRSv infected lymphoid tissue.
Following natural infection, most pigs are resistant to subsequent infection but the mechanisms of protective immunity are not understood. It has been suggested that the immune response to PRRSv has some degree of strain specificity.28 Indeed it has also been suggested that the ability to cross the placenta is also strain specific and that although maternal immunity may not prevent transplacental infection it may exert additional selection pressure.29 Circulating antibodies to the virus are detectable within 14–21 days after infection based on indirect immunofluorescence test or ELISA,30,31 and 15-kDa protein is the most immunogenic of the viral proteins and may provide the antigenic basis for the development of improved diagnostic tests.32 However, this response is not of neutralizing antibodies. These may take a long time to develop. At the same time the occurrence of interferon gamma producing cells is initially weak but this becomes much stronger from 3–6 months after infection. This response may be enhanced by the use of IL-12.33 Several structural, functionally distinct, and specific antibodies to the virus are generated following infection or vaccination. Cell-mediated immune responses specific to the virus also occur.34 The relative role of humoral and cell-mediated immunity in providing protection against disease is unknown.
A unique feature of infection is that viremia and circulating antibodies may exist together; the antibodies protect pigs from re-infection and reduce or eliminate shedding of the virus in the semen of boars. Sows are immune to further disease associated with the virus following recovery from acute infection. Following an outbreak of reproductive disease the level of performance will return to normal, suggesting that immunity develops following natural exposure.35 Protection against subsequent reproductive losses is of long duration in individual animals. However, cross-protection to different strains may not occur. Experimentally infected sows are protected against reproductive losses when challenged with homologous virus over 300 days after initial exposure.36 Extended studies against homologous infection found that the duration of protection was at least 604 days, which is essentially lifelong protection.37 Protective immunity was based on two criteria: the absence of transplacental transfer of challenge virus, and the apparent lack of virus replication in the dam 21 days following inoculation.38
Piglets born from seropositive sows acquire colostral antibodies which decline at highly variable rates from 3 to 8 weeks after birth.39 Passive immunity provides effective immunity for the piglets,40 but loss of passive immunity at various ages results in susceptible pigs and infection that results in persistence of the virus in pigs 6–9 weeks of age, which are considered as the major reservoir of the virus in farrow-finish herds.40 In the absence of natural infection, maternal antibodies become undetectable between 6 and 10 weeks of age.39 Some litters do not have maternal antibodies and may not have detectable antibodies until 4 weeks of age, and clinical disease may occur at 2 weeks of age.31 By 8 weeks of age, antibodies are usually detectable in all pigs and they persist for several months. However, there may be a large variation in the levels of antibodies in piglets at 10–12 weeks of age when they are moved to the finishing units.39 In longitudinal surveys, the seroprevalence of the virus in the 4- to 5-week-old pigs were higher than in the 8- to 9-week-old pigs, and most pigs were negative when they entered the finishing units.41 In herds where the virus persists, sows did not suffer repeated reproductive losses, indicating that some form of protective immunity develops.
The virus has a predilection for immune cells and disease manifestations can be linked directly to changes in the immune system.34 The replication of the virus in the cells of the immune lineage, especially macrophages, may lead to immunosuppression and predispose to secondary infections. Thus immunity to the virus may be a double-edged sword; the virus attacks the immune system, which may cause immunosuppression, while at the same time inducing protective antibodies.
Antibody-dependent enhancement of infection may also occur since low levels of antibody enhance the ability of the virus to enter the pulmonary alveolar macrophage cells and replicate and destroy the cells. This may be important in sucking and nursery pigs exposed to the virus during a period of declining maternal antibody.
Housing of all age groups in one building, introduction of new animals, housing on slatted floors, storage of slurry under floors, exposure to transport vehicles, and lack of disinfection procedures have been suggested as factors that increase the probability of herd infection. Lack of quarantine facilities for recently imported pigs is a major risk factor. There appears to be infrequent spread during warm weather compared to cold weather.42
PPRS virus strains have many identical properties but some antigenic differences. Strains of the virus from the United States and Canada are antigenically similar, and different from the European Lelystad virus isolate.14,43 All the strains appear to be highly infectious.44 There are serological differences between the European and American strains,45 and the antigenic and genomic differences between the North American and European isolates suggests the existence of two genotypes.46 There are different genotypes and at least three minor genotypes within the major US genotype.47 The simultaneous coexistence of the strains has been shown but the significance of the observation is not understood.48 Genetic variations exist not only between European and US strains but among the US isolates, indicating the heterogeneous nature of the virus. Antigenic variation may affect the accuracy of diagnostic tests and the efficacy of vaccines.49 The North American strains have been called type 2 virus. They are continuously varying. The European type 1 virus was thought to be less virulent and less likely to change but this may not be so, as recent isolations show that it is also continuing to change.
Infection with the virus does not always result in clinical disease and the detection of high levels of serum antibody in many herds without history of clinical disease suggests that the consequences of natural and experimental infection depend on a complex of factors associated with host susceptibility and virus virulence. In 2000–2001 there were severe outbreaks in the USA associated with new isolates.50 There are now both European and US strains originating from viral vaccines in Poland.51 The effects of the virus on reproductive performance are strain-dependent.52 Strains of the virus cross the placenta when given to pregnant sows and most sows will remain clinically normal and farrow normally. However, depending on the strain used, the number of late-term dead fetuses from gilts infected experimentally at 90 days gestation may vary widely, and all gilts become viremic and develop antibody.52 There are also marked differences in pathogenicity for the respiratory tract between US strains of the virus compared to the Lelystad virus when inoculated experimentally into 4-week-old cesarean-derived colostrum-deprived pigs.53,54 Some strains cause severe lesions of the lymphoid and respiratory systems, which appear to be the major sites of viral replication.55 The difference in pathogenicity may explain the variation in severity of clinical disease observed in field outbreaks.
Field observations have suggested that the presence of the virus in a herd may increase the susceptibility of animals to other infections. However, studies with sequential infection of the virus followed by experimental inoculation with H. parasuis, Pasteurella multocida, or A. pleuropneumoniae have failed to demonstrate increased severity of disease.56 There is however strong evidence to say that PRRSv predisposes to S. suis.57-60 It may also predispose to Salmonella choleraesuis,61 Bordetellae bronchiseptica,62 or M. hyopneumoniae.63 This view is not universal in that infection with the virus did not increase the severity of experimental Mycoplasma hyopneumoniae infection in young piglets.64 However, in the laboratory investigation of PRDC the most potent combination of agents is PRRSv and M. hyopneumoniae.65,66 A model of the dual infection has recently been described in which M.hyo was shown to predispose to PRRSv infection.67 Based on diagnostic submissions, however, concurrent pulmonary bacterial infections may occur in up to 58% of cases in which the virus was also isolated.68
There is also the possibility that many strains may be found in the same herd, e.g. three strains were found in one herd.69 Several viruses have been found in the same pig and one great authority has expressed the view that each virus in each pig may be different from every other virus.70
A syndrome was described in neonatal pigs marked by neurovirulence. Replication in the brain was verified by IHC in brain sections. Meningoencephalitis induced by the virus was unusually severe.71
Virus is produced rapidly after infection probably within 12 hours.72 The virus was shown to evolve continuously in infected pigs, with different genes of the viral genome undergoing various degrees of change.73
There are unlikely to be any wildlife reservoirs (except for feral and wild pigs)61 although infected mallard can still excrete the virus 39 days later.74 Most pigs clear PRRSV within 3–4 months but some may remain persistently infected for several months.75,76 The antibody response does not reflect the carrier status. It is possible that cytokines can switch the balance from a sub-clinical infection to disease manifestation.77 There is no evidence that PRRSv is found in the tonsils as a representative tissue.78
The virus spreads rapidly within herds when infected pigs are housed in confinement. Up to 90% of sows may seroconvert within 3 months of the virus being introduced into a closed breeding herd. The mode of spread is presumed to be by direct contact probably nose to nose. The virus generally requires close pig to pig contact to achieve an exposure dose. The virus is present in a variety of biological fluids,74 nasal discharge (positive 21 days later), oropharyngeal scrapings (158 days later), possibly mammary secretions although this probably uncommon especially as previous vaccination does appear to prevent shedding,79 urine (28 days) and feces (28 days), and intranasal inoculation has been used to reproduce the disease experimentally. The feces may be an intermittent source, a usual source, or not a source.80 The virus is present in saliva and, considered in the context of the social behavior of pigs, may play an important role in transmission.81
The virus may persist in, and circulate between, different age groups and locations in a herd for several months despite the absence of clinical disease and may be transmitted by contact to replacement animals or to uninfected farms.82 Infected pigs may remain carriers of the virus for up to 15 weeks.31 Persistent and contact infection can be maintained in a nursery if uninfected pigs are continuously exposed to infected pigs.19 Pigs in the nursery become infected through contact with older infected pigs and not by in utero or postpartum exposure to infected sows.83 Long-term surveys of farrow-finish herds reveal that isolation rates of the virus reach highest level of 70–100% of pigs 6–8 weeks of age, which coincided with the lowest level of maternal immunity.40 If you rely on infected nursery pigs to transmit infection to incoming gilts in acclimatization studies then nursery pigs may only be viremic for a maximum of 60 days.84 There is no association between lymphadenopathy and PRRS viremia in nursery pigs 4 and 6 weeks post-weaning. Viremia cannot be predicted solely on the basis of clinical signs.85 Large finishing enterprises purchasing pigs of variable infection and immune status provide ideal conditions for persistent virus circulation. Breeding herd subpopulations of infected pigs may exist, and perpetuate and enhance the infection in a herd. The inability to control such subpopulations may reduce opportunities for successfully controlling the disease.21
Infection may persist for an extended period of time because of:
• Incomplete infection of the susceptible population during the acute phase
• Introduction of susceptible breeding stock
• A persistent viral infection in individual pigs with the potential of shedding virus under certain conditions, such as grouping for weaning or farrowing
• A rapid decline in passive immunity in young pigs; and variable periods of active immunity.
Genetic randomness of isolates does not correlate with geographical distance. Movement on to the farm of PRRSv does not generally occur by distance limited processes such as the usual wildlife vectors but more typically occurs because of long distance transport of animals or semen.86
Spread between herds is associated with the introduction of infected carrier pigs. Infected boars may shed the virus in their semen for up to 40 days after experimental infection. In boars the virus can be found in semen by PCR for much longer periods than can be found in the blood by virus isolation or antigen detection and the likelihood is that monocytes enter the bulbourethral glands which then contaminate the semen.87 Following experimental infection of sexually mature boars the virus was present in the semen 3–5 days after infection, and on days 13, 25, 27, and 43.88 Using a PCR assay the virus can be detected in semen for up to 92 days after experimental infection.89 The insemination of gilts with semen from experimentally infected boars resulted in clinical signs of disease and failure to conceive.90 Following artificial insemination of gilts with semen from experimentally infected boars, the gilts will seroconvert.91 The use of the modified-live PRRS virus vaccine in boars is controversial because some boars may still shed wild-type virus in semen after challenge exposure 50 days after vaccination.92 The inoculation of PRRSv negative replacement gilts with serum from nursery pigs presumed to be viremic resulted in seroconversion of all 50 gilts tested.93
Exposure of pregnant gilts to either attenuated (vaccine) or virulent (field) strains of the virus can result in congenital infection.94 Congenitally infected pigs can support virus replication for a long period of time during which the viral replication is confined to the tonsils and lymph nodes.95 After 260 days there were no serum antibodies and between 63–132 days there was no evidence of virus in the lung.95 Vaccine and field strains can be transmitted postnatally from infected to non-infected littermates. Pigs infected with field strains have an inferior rate of survival and growth than do non-infected pigs. This suggests that use of attenuated virus vaccine during gestation is questionable.
The disease has occurred in PRRS-seropositive herds in Denmark with no previous clinical evidence of PRRS virus. These herds were then vaccinated with a modified live virus vaccine licensed for use in pigs 3–18 weeks of age.96 Boars entering artificial insemination units were also vaccinated. Following vaccination, a large number of herds experienced an increased number of abortions and stillborn piglets, and an increasing mortality in the nursing period. The problems occurred mainly in herds without clinical signs among sows, and with sows with low antibody titers in the period immediately before vaccination. The PRRS virus was isolated from fetuses and identified as the vaccine virus. The evidence suggested that the vaccine virus had spread to non-vaccinated sows followed by transplacental infection of the fetuses. Spread of the vaccine virus was also demonstrated in a non-vaccinated and previously virus-free breeding herd.
Possible routes of transmission include:
• Introduction of vaccinated animals
• Use of semen from vaccinated artificial insemination boars
• Aerosol transmission. Although an experiment failed to transmit infection from pigs to pigs in a trailer parked 30 meters away97 there is a suggestion that it is transmitted for a short distance but this possibly only occurs intermittently98
• Others. Fomites and infected personnel were shown to be capable of transmitting the virus following contact with infected material. Infected hands, boots and protective clothing can do it99
Needles will transmit the virus100
People do not usually act as vectors101
Mosquitoes were not seen in one study to be a likely vector for PRRSv102,103
Houseflies. The intestinal tract of houseflies will support infectious PRRSv for up to 12 hours following feeding on an infected pig but only for a short period of time on the surface of the fly.104 Houseflies may transmit PRRSv within a herd of pigs and potentially between pig farms.105
Airborne spread across regions and between countries is suspected. In Europe, during the winter of 1990/91, the infection appeared to spread by the airborne route from Germany, across The Netherlands and into Belgium. Low temperatures, low sunlight, and high humidity may have facilitated airborne spread. Airborne spread up to 20 km has been suggested but most airborne spread is probably limited to less than 2 km. Usually it is difficult to transmit the agent one meter.106,107 One author thinks that it may be capable of being transmitted 150 meters.108
A study in France of a series of outbreaks showed that 56% of the herds were infected through pigs, 20% through semen, 21% through fomites and the source was unknown in 3% of cases.109 Epidemiological investigations in Belgium attribute 70% of herd infections to local spread, 9% to purchase of infected pigs, 4% to other contacts, and in 18% of cases the source of infection could not be determined. There is no evidence that rodents are susceptible to infection with the virus and are probably not a reservoir for the virus.110
Most spread between herds occurs by the introduction of unknown infected breeding stock into herds previously uninfected. Primary infections are common in multiplying herds which supply unknown infected replacement gilts to other farms.
The PRRS virus is fairly labile and does not survive for more than 1 day on solid fomites, but for several days in well and city water.111 It may survive for several years in deep frozen tissues, but only 1 month at 4°C, 48 hours at 37°C and less than 45 minutes at 56°C. There appears to be a low risk from contaminated lagoon water and the viability of PRRSv in swine effluent is relatively short (1–8 days) although this is very temperature dependent.112
Pig meat does not retain detectable amounts of the virus and it is unlikely that the transmission through meat occurs.113
It is likely that piglets born with infection from in utero infection probably may remain viremic for ever even in the face of antibody formation. Neonatal infection is probably cleared slowly but infection in the older animal may be cleared much more quickly.
The export market for pork from a country can be seriously affected when a disease such as PRRS occurs. When the disease was recognized in the United States, countries such as Mexico, Japan, Canada, and South Korea banned the importation of pork from the United States, or required certification that the swine originated from premises where, within the 30 days prior to the issuance of the health certificate, no swine were introduced from a municipality in which a premises infected with the virus is located.
The economic losses may be very high because of stillbirths, abortions, small litter sizes, birth of weak pigs, which increases preweaning mortality, and increased non-productive days. In weaned pigs, losses are associated with respiratory disease. In addition, there are the costs of control which may be high, dependent on the control strategies undertaken. Typically, about 20% loss in annual production can be expected from a severe outbreak.
Negative weaned pigs had an increased margin per pig of $2.12 over the pigs minimally affected by PRRSv in the nursery but which seroconverted in the finishing herd, and $7.07 over the pigs with persistently circulating PRRSv in the nursery.114
Many piglets are probably infected in utero. This infection modulates the leukocyte subpopulations in peripheral blood and bronchoalveolar fluids.115,116 Following infection the number of CD8+ cells increased in systemic lymphoid tissue whereas numbers of B-cells increased in mucosal associated lymphoid tissue.117 Virus infection induces a simultaneous polyclonal activation of B-cells mainly in the tonsils and an exaggerated and prolonged specific humoral immune response due to persistent viral infection in lymphoid organs.118 Piglets surviving in utero infections have a high count of CD8+, CD2+, CD4+CD8+, SLA-class II cells in the peripheral blood.119 The cytokine changes have been described.120-122 Persistent infection occurs in these pigs.123 Virus appears to persist in the lymphatic organs and particularly the tonsils and the lungs.124 Lymphoid tissue tropism occurs during persistent infection when the piglets have been exposed in utero.125 There may be a PRRSv ligand for a cell surface heparin-like receptor on pulmonary alveolar macrophages.126 It has been shown that PRRSv entry into the alveolar macrophage involves attachment to a specific virus receptor followed by a process of endocytosis, by which virions are taken into the cell within vesicles by a clathrin dependent pathway.127 The alveolar macrophages when infected round up, show bleb formation and eventually rupture.128 TNF α released from damaged macrophages after PRRSv infection may induce apoptosis in uninfected lymphoid cells.129 In a study of cells in the lungs it was found in both non-infected and infected cells. The majority of the apoptotic cells were non-infected. The peak of apoptosis was at 14 days and was preceded by a peak of IL-1 and IL-10 production at 9 days post-infection.130 The PRRSv infection directly interferes with type 1 IFN transcriptional activation.131
Neonatal or nursery infection is probably through the virus reaching the nasopharyngeal epithelium following inhalation from the nose to nose contact with other pigs. It is then probably removed to the tonsils where they are internalized into cells of the macrophage/monocyte series.
As few as 10 or even fewer virus particles inoculated into the nose or given intramuscularly will infect a pig.132 The virus may enter the cell through an endocytic pathway133 or through a virus receptor.134 A third possibility is that the virus may enter the cell through an antibody-dependent enhancement with virus-antibody complexes entering the cell through Fc receptors on the cell surface.135
Initially, a viremia occurs, with subsequent distribution and multiplication of the virus in multiple body systems and organs causing interstitial pneumonia, vasculitis, lymphadenopathy, myocarditis, and encephalitis.136 Alveolar macrophages are primary targets for virus multiplication but this does not fully explain the pathogenesis.34 Multiple glycoproteins appear to be involved in infection of pulmonary alveolar macrophages.137 Possibly up to 40% of alveolar macrophages are destroyed.138 Whether it is a particular group that is damaged or not or all the alveolar macrophages is not known but after about 28 days there is a resumption of normal alveolar macrophage function. PRRSv causes the apoptosis of alveolar macrophages and pulmonary intravascular macrophages.139 The increase in IFN gamma positive cells correlated well with the severity of the lung lesions which may be because of the presence of PRRSv in the lung.140 IFN gamma markedly inhibits the replication of PRRSv in macrophages.141 The effects of the virus on the immune system may explain the suspected immunosuppression and secondary infections, which are recognized clinically but have not been reproduced experimentally. The cytokines IL-10 and IL-12 are expressed in inflammatory lesions in the lung and play an important role in the defense against PRRSv.142 In utero infected pigs showed significantly increased IL-6, IL-10 and IFN gamma mRNA expression (IL-2, IL-4 and IL-12 remained the same) and this was concurrent with a significant decrease in the number of CD4+CD8+ T-cells.121 The cell mediated and cytokine message profiles returned to normal levels similar to those of control pigs by about 10 weeks of age. The induction of the IL-10 response may be one of the strategies used by PRRSv to modulate the host immune responses.143 Increases in IL-4, gamma IFN and TNF α were found in the lymphocytes of infected piglets but IL-8 showed a decrease.120 Other authors have the opposite views144 who showed that T-cells showed an increase in CD8+CD4+ and CD4−CD8+ subsets within activated cells, whereas CD4+CD8− cells decreased with time. T-cells responding to the virus showed a Th1 type cytokine production pattern.145 These authors also reported a decrease in TNF-α and a decrease of IL-1-α and macrophage inflammatory protein which are contrary results to the above. Perhaps this is the key to PRRSv infections in that all pigs may respond differently. There may be either depressive or stimulatory effects.146,147 The imbalance of IL-12 and IL-10 produced in PRRSv infected pigs may favor the humoral responses and suppress cell mediated immune responses for the first 2 weeks of life.148
There was also a temporary immunosuppression in piglets at about 4 weeks post-infection. Vascular lesions associated with PRRS virus infection are analogous to those observed in horses with equine arteritis virus, also a member of the Arteriviridae family,149 and the renal lesions of equine viral arteritis infection correspond to those of PRRS. Inflammatory infiltrates are seen at the junction of the renal cortex and medulla, with vascular changes associated with the muscular tunics of small arterioles.
The characteristic lesions can be reproduced in conventional pigs at 1, 4, or 10 weeks of age, and the variation in severity of clinical disease can be attributed to differences in strain virulence.54,150 The effects of the virus on reproductive performance are also strain-dependent.52 There is no evidence that virus will grow in the ovarian tissues but may be taken into them by circulating macrophages. PRRS virus can replicate in the testicular germ cells151 but there is no evidence that there is any PRRSv in ova indicating that the female gonad is resistant to persistent infection.152 Some strains are of low pathogenicity, while others are highly pathogenic.153 The reproductive disease has been reproduced experimentally and the effects on the fetus are dependent on the stage of gestation. Aerosol exposure of non-immune pregnant gilts to the Lelystad virus in late gestations (84 days) results in clinical disease.154 After an incubation period of 4–7 days, all sows are inappetent and listless for 6–9 days. Some sows develop blue-colored ears accompanied by abdominal respirations. Sows may farrow at days 116 and 117 of gestation, giving birth to dead, mummified, and live piglets. Many of the live-born piglets are pale, listless, and weak, and some are in respiratory distress and exhibit varying degrees of splayleg or muscular tremors. The virus may be isolated from stillborn piglets or those born alive. Antibody is present in precolostral serum samples or ascitic fluids of piglets, which demonstrates transplacental passage of the virus.
The gross and microscopic lesions in the fetuses from sows experimentally infected oronasally with the virus at 90 days of gestation consist of hemorrhage of the umbilicus and necrotizing umbilical arteritis with periarterial hemorrhage.155 Severe pulmonary lesions are present in fetuses inoculated in utero with the virus between 45 and 49 days of gestation.156 Even the lowest PRRSv exposure dose102 caused reproductive failure in naïve, unvaccinated animals.157 When sows are inoculated oronasally with the virus in mid-gestation the virus does not readily cross the placenta, but replicates in fetuses that are inoculated directly in mid-gestation.158 It is suggested in prenatal piglets that PRRS replicates primarily in lymphoid tissues, having gained access to the them from the placenta via the bloodstream.159 Thus the fetuses are more susceptible in late gestation than earlier in mid-gestation,160 or there is greater likelihood of transplacental infection during late gestation.161 Experimentally, the intrauterine inoculation of the virus into gilts on the day after natural breeding may have little or no effect on their reproductive performance.162 There appears to be no direct or indirect effect on luteal function contributing to PRRSv induced abortion.163 The virus may cause cell death directly such as the alveolar macrophages, or in lymphoid tissues. PRRSv affects Marc 145 cells which undergo necrosis at a much higher rate than apoptosis, and increases with virus levels used to infect the cells.164 Apoptosis does occur in PRRSv infected cells but it is a late event during PRRSv replication and rapidly results in a necrotic-like death.165 Lesions have been seen in the placenta and in the vessels of the umbilical cord but these are rarely reported with European strains although they may be more common with the USA strains.
The original descriptions of porcine necrotizing pneumonia (PNP) were associated with swine influenza but more recent research has shown that PRRSv is consistently and predominantly associated with PNP and should be considered the key etiologic agent for PNP together with PCV2.166
The main feature of clinical disease associated with this virus was the extreme variability of the clinical signs. In general signs associated with PRRSv appear to result from a combination of genetic factors and herd management characteristics. The relative influences of these two factors differ depending on the specific clinical signs in question.167 These may vary from inapparent infection to sudden death and abortion storms (the sow abortion and mortality syndrome). Its synergism with PCV2 is in doubt. It does not seem to be potentiated by the other great pig pathogen PCV2 virus168 on one hand but on the other hand, others think it increases the severity of PRRSv induced interstitial pneumonia.169 It may be that PRRS infection enhances PCV2 replication.170 It is predisposed by M. hyopneumoniae and this can be reduced by vaccination for M. hyopneumoniae.171 In turn PRRS predisposes to Bordetella bronchicseptica.172,173 Both may interact to reduce the efficiency of lung defense mechanisms and facilitate infection with P. multocida. There is little effect on H. parasuis secondary infection with a slight increase in macrophage uptake of HPS during the early infection which is reduced after 7 days.174 There is evidence that concurrent infection with TGEv and PRRSv is likely to have little or no effect on subsequent shedding or persistence of infection.70 Infection with PRRS is common in pigs with PMWS but there is no evidence that PRRS is necessary for the development of PMWS.175 PRRS has been seen in a swine herd with PCMV.176 Synergism between PRRSv and Salmonella choleraesuis has been described with unthriftiness, rough hair coats, dyspnea, and diarrhea. Pigs that received dexamethasone were the most severely affected and half died but they also shed significantly more organisms in feces and also had significantly higher PRRSv titers.177 Simultaneous infection between PRRSv and S. suis is much more severe than with either agent on its own.178 PRRSv induced suppression of pulmonary intravascular macrophage function may in part explain PRRSv associated susceptibility to S. suis infection.179
There is also a clear synergism between PRRSv and LPS in the exhibition of respiratory signs in conventional pigs.180,181 In these joint infections the rise in TNF-α, IL-1, and IL-6 were 10–100 times higher than in the single infections.181 Reproductive failure and respiratory disease are the major clinical findings which are also highly variable between herds. All age groups in a herd may be affected within a short period of time.
Pigs infected with both PRRSv and M. hyopneumoniae had a greater percentage of pneumonic lung, increased clinical disease and lower viral clearance182 than pigs with single infections. There were also increased levels of IL-β, IL-8, IL-10, and TNF-α in lung lavage fluid and this may be the way that the joint infection increases the pulmonary response.
If 90-day gestational gilts are given vaccine or field strains of PRRSv then some pigs are born dead, most pigs survive and some pigs were infected in utero. Vaccine strains did not affect postnatal growth but field strains reduced growth.94 It may be that the virus entered the reproductive tract through the viremia and then the seeded tissues may release the virus back into the serum at low levels.183
Anorexia, lethargy, depression, and mild fever in pregnant gilts and sows are common initial clinical findings affecting 5–50% of animals. This is commonly followed by a sudden increase in early farrowings at 108–112 days of gestation, late-term abortions, stillborn and mummified fetuses, partially autolyzed fetuses, weak neonates with high mortality within a few hours or days after birth, late returns to estrus, and repeat breeders. This is generally followed by mid-gestation abortions, and marked increases in the percentage of mummified fetuses, early embryonic death, and infertility. In large herds, successive groups of 10–20% of gilts and sows may become anorexic over a period of 2–3 weeks. Cyanosis of ears, tails, vulvas, abdomens, and snouts may occur in a small number of sows, and occurs more commonly in European outbreaks and is uncommon in North America. Following the initial outbreak, a ‘storm’ of reproductive failure may occur consisting of premature farrowings, late-term abortions, an increase in stillbirths, mummified fetuses, and weak neonates. This second phase of reproductive failure may last 8–12 weeks. Stillbirths may reach 35–40%. Weakborn piglets die within 1 week and contribute to a high preweaning mortality.
In subsequent times with the European strains there may be just outbreaks of rolling inappetence or occasional early farrowings. However, there are serious clinical outbreaks in Italy, Poland and outbreaks associated with new variants in the UK.184
Reproductive disease may be preceded by, or follow, respiratory disease in the breeding herd, the finishing pigs, or younger pigs. The reproductive aspect of the disease typically lasts from 4–5 months, occupying an entire reproductive cycle within a herd. This is followed by a return to normal performance. Repeated incidents of reproductive failure in individual gilts and sows are unusual but recurrent episodes may occur in herds purchasing replacement gilts that do not have sufficient immunity.185
Outbreaks of the disease are characterized by a period of severe reproductive problems in the breeding herd, followed by a return to near normal reproductive performance, punctuated by recurrent episodes of reproductive failure.186 Most herds eventually return to pre-outbreak levels of reproductive performance but some herds never achieve pre-outbreak performance levels.
Boars may also be affected with anorexia, fever, coughing, lack of libido, and temporary reduction in semen quality.184
The most important problem facing many of the larger pig industries in the world is porcine respiratory disease complex (PRDC). The most important contributor to this syndrome is PRRS virus. The generation of immunity capable of protecting pigs by mediating virus inhibition through virus neutralizing antibodies or interferon takes time.187
Disease occurs in pigs of any age, but especially in nursing and weaned pigs, and is characterized by anorexia, fever, dyspnea, polypnea, coughing, and subnormal growth rates. A bluish discoloration of the ears, abdomen, or vulva may also occur – ‘blue-eared disease’. Death may occur in the acute phase. In some herds up to 50% of pigs are anorexic, up to 10% may have a fever, up to 5% are cyanotic, and up to 30% have respiratory distress. In weanling pigs the morbidity may be as high as 30%, with a mortality of 5–10%. Nursery pigs exhibit respiratory distress and growth retardation. Conjunctivitis, sneezing, and diarrhea are common. All of these signs may appear to move through the various age groups in the herd over several days and a few weeks. The course of the disease in a herd may last 6–12 weeks. In gilts and sows of any parity, anorexia and fever, lasting for several days, are noted initially. The acute-phase respiratory disease may last several months but is often followed by a long period of postweaning respiratory disease which may last up to 2 years. This long course is often accompanied by secondary infections in successive batches of weaned pigs. Unthriftiness may persist throughout the finishing period with an ineffective response to antibiotics and vaccines.
Preweaning morbidity and mortality is a major feature of the disease. Litters are often unthrifty, and many deaths occur within the first week of age.
PRRSv infection significantly increases the number of alveolar macrophages in bronchoalveolar lavage fluid approximately 10-fold between day 10 and day 21 of infection.188 Approximately 63% of the cells were cytotoxic T-cells and natural killer cells. Serum haptoglobin levels were increased from 7–21 days.189
Piglets also become anemic in PRRSv infections and the most highly pneumovirulent strains induced the more severe anemia. This is probably due to a direct or indirect effect on the erythroid precursor cells of the bone marrow.190
A definitive diagnosis requires detection of virus in infected animals, detection of antibodies in fetal fluid, or in precolostral blood of stillborn and weakborn piglets.191 Detection of antibodies in sera of groups of pigs of different ages is also necessary. The most suitable body fluid and tissue samples and diagnostic tests for the etiologic diagnosis of PRRS are dependent on several variables including:
• Age of pigs from which samples are collected
• Stage of infection (acute or persistent)
• Available complement of diagnostic reagents
• Urgency of obtaining results.192
When congenitally or neonatal pigs are affected, both serum and alveolar macrophages are reliable samples. For older pigs, alveolar macrophages are more reliable than serum.
The virus can be demonstrated by isolation using cell cultures, by direct detection of viral antigen in tissue sections, or by the detection of virus-specific RNA.191
Samples used for virus isolation include serum, thoracic fluid, spleen, and lung. Porcine pulmonary alveolar macrophages are used for isolation of virus. Alveolar macrophages using immunofluorescence microscopy can be used for detection of virus during acute infections.193 The PCR assay is a reliable, sensitive, and rapid test for the detection of virus in boar semen.194 It can also be used to determine whether suckling piglets are infected with PRRSv before vaccination and for determining the relationship between parity and shedding of virus.195 It can also be used to obtain PRRSv piglets.196 PCR followed by RFLP analysis using several restriction enzymes provides a good genetic estimate for isolate differentiation.197 A reverse transcription and PCR, coupled with a microplate colormetric assay, is an automated system that is a reliable and easy test for the routine detection of the virus in semen samples from seropositive boars.198 Multiplex RT nested PCR can be applied to formalin-fixed tissues.199
A nested PCR has been described that is 100–1000 times more sensitive than the usual PCR.200
An assessment of the viral load can possibly be made by using the quantitative competitive RT-PCR.201 A quantitative Taqman RT PCR is time saving, easy to handle, less likely to be cross contaminated and highly sensitive and specific.202 Immunohistochemical techniques are available for the detection of virus in formalin-fixed tissues.203,204 The virus was detected in 11–23% of animals with interstitial pneumonia. It was found in 21–31% of animals less than 3 months of age but in only 6–17% of those more than 4 months of age.205 The immunogold silver staining is superior to the immunoperoxidase staining systems for detection of virus in formalin-fixed tissues.206,207 Reverse transcription-polymerase chain reaction (RT-PCR) is also available and can distinguish between North American and European strains.
A double ISH technique has been developed208 which can show both PRRSv and PCV2 and a small number of alveolar macrophages stain for both antigens.
Serological tests have good sensitivity and specificity for diagnosis on a herd level and less so on the individual animal. The tests in common usage are described below. One of the problems is that the serological response to a nonvirulent strain is the same as it is to a virulent strain.204 It is also important to realize that although a positive result for antibody indicates exposure to virus, a negative test does not necessarily mean that the pig is free from PRRSv or has not been in contact with the virus.209
The immunoperoxidase monolayer assay (IPMA) is often the first test used. Approximately 75% of sows infected with the virus seroconvert to the Lelystad virus. However, the IPMA does not allow for large scale surveys.
Indirect ELISA is used for the routine serodiagnosis; it is simple, inexpensive, effective, and a better alternative to the indirect immunofluorescent assay or the immunoperoxidase assay.210 It is suitable for the screening of large numbers of samples and is best used as a herd test.211 Because of marked differences between and within North American and European virus isolates, serological tests using only one antigenic type of the virus may potentially yield false-negative results with antisera against diverse antigenic types of the virus. A mixture of ELISA antigens from North American and European strains gives superior results when both types of viruses are known to exist.212
A meat juice ELISA has been developed which gives complete agreement with the serum ELISAs.213,214
Immunofluorescent antibody (IFA) is a highly sensitive test. Antibody titers are detectable in infected pigs 8 days after inoculation. The IgM IFA test is also a rapid and simple test for diagnosing recent infection as early as 5–28 days after infection in 3-week-old piglets, and 7–21 days in sows.215
This test is useful for the detection of later and higher levels of antibody when the conventional methods cannot detect antibody. The test can differentiate between strains.216 The serum neutralization test is not used for routine diagnosis191 because neutralizing antibodies do not appear early on in the infection.217
The serological diagnosis must be used and applied on a herd basis, and acute and convalescent sera submitted for optimal results. A baseline herd sampling is necessary to evaluate the status of a herd and to determine if and in which groups the virus is circulating. In large herds of over 500 sows, samples are taken from 30 animals in each breeding, gestation, and farrowing group, with representation from all parities. In addition, 10 nursery pigs (5 weeks old), 10 pigs at the end of the nursery period, and 10 pigs in late finishing stage constitute a herd profile. Thus, serological monitoring can be used to monitor the circulation of virus within a closed herd and to determine infection status of breeding animals which are to be introduced into seronegative herds.218 Results from the sow sera indicate if the sow herd is virus-negative, stable, or has an active virus circulation. Comparison of the early and late nursery pigs indicates if the virus is circulating in the nursery. Comparing the nursery results with the end of the finishing period indicates if the virus is circulating in the finishing groups of pigs. IFA titers in pigs range from 1:256 to 1:1024 by 2–3 weeks after infection. Titers decline over 3–4 months unless reinduced by exposure to circulating virus. Uninfected nursing pigs are negative or have maternal antibody. Seropositive 9 to 10-week-old pigs leaving the nursery indicate virus circulation in the nursery. If pigs leaving the nursery are negative, and positive later in the finishing unit, virus circulation is occurring in the finishing unit.
Sera from outbreaks of the disease in the United States, Canada, and Europe have been compared, and although the isolates from both continents are closely related, the strains isolated in the United States and Canada are more closely related serologically than they are to the European strains.
A series of postmortem examinations of different aged pigs obviously from different stages of production will tell you what is going on over time. A series of such examinations will probably tell you more than any other investigations.
No characteristic gross lesions are present in sows, aborted fetuses or stillborn piglets. Microscopic lesions which may be present in aborted fetuses include vasculitis of the umbilical cord (not recorded in European strain infections) and other large arteries, myocarditis, and encephalitis.219,220 Unfortunately, none of these changes is present consistently, and the majority of fetuses and placentas are histologically normal. These lesions are all more common in the North American virus infections.
In suckling and grower pigs, infection with the PRRS virus is usually characterized by an interstitial pneumonia. The PRRSv affects both pulmonary intravascular macrophages which may be important as a replication site and alveolar macrophages.221 Loss of bactericidal function in pulmonary intravascular macrophages may facilitate hematogenous bacterial infections. When Danish isolates were injected into piglets, PRRSV was isolated from the lungs and/or tonsillar tissues from both dead and culled piglets under 14 days of age.222 Tracheobronchial and mediastinal lymph nodes are usually enlarged and firm. The gross pulmonary changes vary from lungs that appear normal but fail to collapse, to lungs that are diffusely red, meaty, and edematous. Porcine proliferative and necrotizing pneumonia has been linked to infection with PRRS virus, although the involvement of an unidentified co-pathogen cannot yet be discounted. Grossly, this form of pneumonia appears as confluent consolidation of the cranial, middle, and accessory lobes, together with the lower half of the caudal lobe. Affected lobes are red-gray, moist, and firm (meaty) in consistency. On cross-section, the affected lobes are bulging and dry, and the pulmonary parenchyma appears similar to thymic tissue.
In general histological lesions in piglets are focal non-suppurative inflammatory conditions particularly in the lung and heart.222 Most of the cells undergoing apoptosis do not have markers for PRRSv which suggests that there is an indirect mechanism for the induction of apoptosis.223
Histologically, in addition to marked proliferation of type II pneumocytes in alveoli, there is severe necrosis of bronchiolar epithelium, with necrotic cellular debris plugging the airway lumina.
In the less severe and more common forms of PRRS pneumonia, the alveoli contain protein-rich fluid and large macrophages, some of which may appear degenerate. There is patchy thickening of the alveolar septa, due to infiltrating mononuclear leukocytes and mild, type II pneumocyte hyperplasia. Lymphoplasmacytic cuffing of arterioles is common and syncytial cells are occasionally seen. In field outbreaks, it is usual for the lung pathology to be complicated by concurrent respiratory pathogens.
Microscopic lesions may be found in many other tissues and include multinucleate cell formation within lymph nodes, infiltrates of lymphocytes and plasma cells in the heart, the brain, and the turbinates, plus a lymphocytic perivasculitis in various sites.18,224 Thymic lesions include severe cortical depletion of thymocytes.225 An in situ hybridization technique is a rapid, highly specific, and sensitive detection method for the diagnosis of PRRS virus in routinely fixed and processed tissues.226 Immunohistochemical techniques can also be used to detect the virus in neurovascular lesions.227 PRRSv and reovirus 2 have been found in brain, lung and tonsil by inoculation into Marc 145 and CPK cells.228 Immunohistochemistry on one section would give a positive in 48% of cases, but if five sections were studied then there are positives in >90% of PRRSv infected pigs. If the animals are vaccinated then the positives fall to 14%.229
• Histology – lung, tonsil thymus, thoracic lymph node, brain, kidney, heart, (umbilicus from fetus) (LM, IHC)
• Virology – lung, thoracic lymph node, tonsil (ISO, FAT, PCR).
Respiratory disease must be differentiated from:
• Porcine respiratory coronavirus
• Enzootic pneumonia (Mycoplasma hyopneumoniae)
• Actinobacillus pleuropneumoniae
Reproductive disease must be differentiated from other causes of abortion, stillbirths, and weak neonates in pigs:
• Fumonisin, a recently identified mycotoxin produced by Fusarium moniliforme, has been associated with the appearance of PRRS in swine herds in the United States.
A definitive diagnosis requires a detailed epidemiological investigation of the epidemic including a detailed analysis of the breeding and production records for the previous several months, and the submission of tissue and serum samples for laboratory investigation.
There is no specific treatment against the virus. In outbreaks of respiratory disease, mortality can be reduced by insuring that the environmental conditions in the barns and pens are adequate, the stocking density is kept low, and the feeds and feeding program are monitored. Routine procedures such as tail docking, iron injections, castrations, teeth clipping, and cross-fostering should be delayed or not done during the acute phase of the disease. Supplemental heat for neonatal pigs should be provided if necessary. Sows that have aborted their litters should not be bred until the normal time of weaning. This will reduce the incidence of infertility common at the first estrus after the abortion or premature farrowing. Culling of sows should be minimized and weekly breedings increased by 10–15%. Replacement gilts may be introduced into the premises for exposure to infection before breeding. The consequences of boar infertility and low libido may be minimized by use of artificial insemination or by using multiple sires on each sow. Recurrent illness and secondary infections in weaner and growing pigs can be continuing problems for a few months after an acute outbreak. Reducing the stocking density and an all-in all-out strategy have been successful to reduce the chronic problem. If there is the possibility of treating secondary infections then this should be undertaken. Serum inoculation of naïve gilts has been described and this was shown to be capable of stabilizing sow herds and as shown by the production of negative weaned pigs.230
Control of PRRS is difficult, unreliable, and frustrating because of the complexity of the disease; the uncertainty of some aspects such as immunity, persistence, diagnosis, and the lack of published information based on control programs which have been evaluated under naturally-occurring field conditions. Much of the information available on control is anecdotal and not based on well-designed control programs that can be compared and evaluated. A major problem is the difficulty of obtaining a definitive etiological diagnosis when presented with young growing pigs with respiratory disease and the possibility that other pathogens could be involved. The diagnosis of reproductive failure in gilts and sows is also commonly uncertain.
Some characteristics of the disease are important in planning control programs for individual herds:
• Infection is highly contagious and is transmitted by direct contact. Non-immune pregnant gilts and sows, and young pigs, are highly susceptible to infection resulting in large economic losses
• Infection of breeding stock results in immunity. The efficacy of vaccination is not well-established
• Maternal immunity is present in piglets born from seropositive sows
• Infection can persist for many weeks and months in individuals and in subpopulations of animals
• Infections are usually introduced into a herd by the introduction of infected pigs.
There are two main options for control: eradication of the virus from individual swine herds; and controlling the disease in individual herds to create a stable positive system that allows you to live with the disease. Controlling the disease requires developing strategies to make pigs immune to the infection by controlling infection pressure in the herd and inducing naturally acquired immunity in the herd, or inducing acquired immunity through vaccination. The recommendations for control set out here are guidelines that can be applied and modified to meet different circumstances.
Eradication of the virus from the herd by depopulation of the entire herd followed by repopulation with virus-free breeding stock is biologically possible, but in most cases is impractical and too expensive. Obtaining virus-free breeding stock is usually not possible and, if possible, the herd is highly susceptible to accidental reinfection.
Control within a breeding herd is based on the observation that pigs commonly seroconvert to the virus during the nursery period. Pigs are seronegative shortly after weaning, but 80–100% are seropositive at 8–10 weeks of age.83 A control program based on a nursery depopulation consists of emptying the nurseries and moving all of the pigs to off-site finishing facilities or selling them as feeder pigs.231 Test and removal has been described.232 This is combined with batch farrowing and weaning at intervals of at least 3 weeks.19 The nurseries are completely emptied, cleaned three times with hot water and disinfectant, the slurry pits are pumped out after each cleaning, and the facilities are kept empty for 14 days, during which time all pigs weaned are moved to off-site nurseries, and after which the conventional flow of pigs into the cleaned facilities are resumed. The control program can result in significant improvements in both average daily gain and percentage mortality but it will not eliminate the virus from the herd.231 Using a partial budget model to measure the profitability of nursery depopulation, the financial consequences indicate that it is a profitable strategy to improve pig performance in herds affected with the virus.233 Additional income is generated by the increased number and weight of marketable pigs, as a result of their increased growth rate and decreased mortality. Lower treatment costs reduce overall expenses but there are additional costs due to extra feed necessary to raise the additional pigs and the costs required to house the depopulated pigs. However, it is possible that the economic benefits are due to the control of other pathogens and not merely the PRRS virus.
The details for a nursery depopulation and clean-up protocol for the elimination of the virus are shown in Table 21.2.234
Table 21.2 Nursery depopulation and clean-up protocol for elimination of PRRS
| Day | Procedure |
|---|---|
| 1 | Empty all nurseries, off-site wearing, pump out slurry pits, clean and wash rooms with hot water (>95°C), and disinfect with formaldehyde-based product. Allow disinfectant water to remain in pits overnight |
| 2 | Pump out pits, repeat washing procedure, and disinfect in phenol-based product. Allow disinfectant to remain in pits |
| 3–11 | Allow facility to remain vacant |
| 12 | Pump out slurry pits, repeat washing procedure, and disinfect with formaldehyde-based product |
| 13 | Allow facility to remain vacant |
| 14 | Resume conventional flow of pigs into clean nurseries |
Management of the gilt pool is the single most important strategy for long-term effective control. Controlling the infection in the breeding herd is a prerequisite to controlling infection in the nursery and finishing pig groups. Strategies like partial depopulation and piglet vaccination are ineffective unless the breeding herd is first stabilized, preventing piglets from being infected before weaning. Replacements are a major source of introduction of the virus and activating existing virus in the breeding herd. They also initiate the formation and maintenance of breeding herd replacements.
Subpopulations are subsets of naive or recently infected gilts or sows which co-exist within chronically infected herds. These subpopulations perpetuate viral transmission in the breeding herd and farrowing units, which ultimately produces successions of infected piglets prior to weaning. Modifications in gilt management that may minimize subpopulations include ceasing introduction of replacement animals for a 4-month period, beginning to select replacements from the finishing unit, or introducing a 4-month allotment of gilts at one time.
Exposure to the virus in the breeding herd can be controlled by managing the gilt pool using two strategies.235 In one strategy, herds may be closed to outside replacements, and replacement males and females are raised on the farm. In the other strategy, replacement gilts are held in an off-site holding facility from 9 to 12 weeks of age until breeding age at 7–7.5 months, or even much earlier. This is combined with nursery depopulation as described above. Prior to entry of the gilts into the herd they are serologically tested for evidence of seronegativity or a declining titer, which is required for entry into the herd. The gilts are isolated and quarantined for acclimatization for 45–60 days. This may be combined with two vaccinations, 30 days apart, after entering quarantine. This method reduces the risk of introducing potentially viremic animals into the existing population. The method selected will depend on the production system, management capabilities, and facilities available on each farm. The introduction of younger gilts, in larger groups, less frequently throughout the year, is being recognized as the most effective method for introducing replacement stock to virus-infected herds and long-term control of the disease.
The presence of subpopulations of highly susceptible breeding animals in the herd can be a major risk factor for maintaining viral transmission within problem herds and may explain recurrent outbreaks of reproductive failure. By intentionally exposing all members of a population to the virus it may be possible to eliminate subpopulations and produce consistent herd immunity.21 In endemic herds, exposure of gilts to the virus prior to breeding is critical for prevention of reproductive failure. Seronegative replacement gilts can be introduced into seropositive herds at 3–4 months of age to allow for viral exposure before breeding. If the status is uncertain, quarantine and exposure to nursery pigs of the importing unit is a suitable policy if replacement gilts are bought in before they are bred. It is possible to convert a PRRS positive unit to a negative herd by managing the gilt pool and regulating the pig flow. It appears that PRRSv infection eventually either disappears or becomes inactive in the donor gilt population.236 Similarly serum from nursery pigs (thought to be PRRSv viremic) given to negative replacement gilts resulted in seroconversion of all 50 gilts receiving the serum.237
When outbreaks of the disease occur in nursing piglets, and virus circulation is occurring continuously in the farrowing facility, the following are recommended:
• Cross-foster piglets only during the first 24 hours of life
• Prevent movement of pigs and sows between rooms
• Eliminate the use of nurse sows
• Euthanize piglets with low viability
• Minimize injections of suckling pigs
• Stop all feedback of pig and placental tissues
• Follow strict all-in all-out pig flow in the farrowing and nursery rooms.
These are similar to the system developed in the USA called the McRebel system. This was a method of control which showed that cross fostering of piglets should be minimal within the first 24 hours and banned after this time.238
Feedback has been tried although there are a lot of reasons not to do so. Minced whole piglets were fed to sows and the herd then closed for 23 weeks. No clinical signs were observed. One third of the sows present at the time of the outbreak were still seropositive 20 months after the deliberate infection.239 Disinfection at cold temperatures was described.240
Standard methods, such as quarantining and serological screening of imported breeding stock and restrictions on visitors are recommended to keep units free of infection. Control of infection between herds depends on restricting the movement of pigs from infected herds to uninfected herds. If pigs have to be bought in, then seropositive animals should be imported into seropositive herds. Only seronegative boars should be allowed entry into artificial-insemination units.
Vaccination is an aid to management in developing effective immunity. The goal is to produce a constant level of immunity across a defined population. This effectively immunizes the entire population and eliminates the non-immune, susceptible subpopulations. Vaccination is most effective when used in replacement gilts combined with adequate isolation and acclimatization, and in sows after farrowing and prebreeding. The routine vaccination of sows is not economically viable in herds affected with PRRS virus.241 The vaccine is best suited for stabilizing the herd and is a necessity prior to nursery depopulation or commingling segregated early weaning piglets from virus-positive herds. Vaccination is also intended to produce protective immunity in weaned and growing pigs. The PRRS virus exists in many forms and therefore the closer the genetic make up between the immunizing virus and the challenge virus the better.159
Both inactivated and modified live virus vaccines are available. Killed vaccines may not produce a measurable antibody response stimulation and activation of lymphocytes does occur and any subsequent exposure with vaccine or field virus increases that response. There is no possibility of producing a viremia and no chance of producing shedding and there are no detrimental effects on the host. However there is no evidence that killed vaccines protect against heterologous challenge.
A killed, oil-adjuvanted vaccine based on a Spanish isolate of the virus is intended for protection against reproductive disease in gilts and sows. Initial vaccination involves two vaccinations, 21 days apart, with the second vaccination at least 3 weeks before breeding and with booster vaccinations recommended during subsequent lactations. Experimental challenge provides 70% protection based on pigs born alive and surviving to 7 days.
Modified live vaccines do give a safe and efficacious protection against a wide variety of heterologous challenge strains.242 The vaccine virus can be transmitted from vaccinated to naïve pigs.94,96,243 and to naïve herds. Vaccination of boars causes the virus to be shed244 but if they have been previously exposed and then are vaccinated then there is no release of virus.245
The live vaccine given to finishing pigs will protect against respiratory infections.246
A modified live virus vaccine given once is safe for use in pregnant sows, and vaccine virus is not transmitted to susceptible contact pigs. In growing pigs, vaccinated at 3–18 weeks of age, the vaccine elicits protective immunity within 7 days which lasts 16 weeks. Compared to controls, vaccinated animals have a reduced level of viremia, their growth rates are superior, and they have a reduced number of lung lesions. Field trials suggest that the vaccine provides protection to nursery pigs in units with endemic infection. Live viral vaccines in sows may or may not be a good idea247 as they demonstrated that reduced numbers of pigs were born alive and there were increased numbers of stillborn piglets to vaccinated sows irrespective of stage of vaccination. Both single strain and multistrain vaccines can be attenuated and be useful immunogens but additional studies are needed to make sure that the multistrain vaccines can be recommended for routine field use.248
In Denmark in 1996, the use of a modified live virus vaccine licensed for use in pigs 3–18 weeks of age was used in a large number of PRRS virus-seropositive herds.96 Following vaccination, a large number of herds experienced an increased incidence of abortions, stillbirths, and poor performance during the nursery period. The vaccine virus was isolated from fetuses and it was concluded that the virus was transmitted to seronegative non-vaccinated pregnant gilts and sows (see Methods of transmission). The viruses were collected and sequenced204,249 and shown to have a 60% homology to Lelystad but a 98.5% homology to the USA strain ATC-2332 the USA reference strain. It was therefore thought that the vaccine viruses were reverting to their natural antecedents and their virulence.250-252 Describing the vaccine virus it was shown that given to piglets it could infect non vaccinated sows. Given to sows it can produce congenital infection, fetal death, and an increased pre-weaning mortality.252
The vaccine virus can be maintained in the population where it may undergo considerable genetic change and then lead to the establishment new variants. Vaccination with the US type vaccine produces little effect on viremia with EU PRRSv. Vaccination with EU type vaccines produced complete suppression of EU PRRSv isolates.253
A modified live virus vaccine has been evaluated in pigs vaccinated at 3 weeks of age and challenged at 7 weeks of age.254 Efficacy was evaluated using homologous and heterologous strains of virus known to cause respiratory and reproductive disease. The vaccine controlled respiratory disease but did not prevent infection and viremia. There are no published reports of randomized clinical trials evaluating the vaccines under naturally occurring conditions. In many cases of PRDC vaccination fails simply because it was given too late or because there was no cross protection to heterologous strains.
DNA vaccination is said to produce both humoral and cellular responses and neutralization epitopes on the viral envelope glycoproteins encoded by ORF4.255 Possibly recombinants can be used as vaccines.256
The use of an attenuated virus vaccine in boars results in a marked reduction in viremia and shedding of the virus in semen compared to non-vaccinated control animals.257 Introducing a vaccination program using the live virus vaccine may be considered as a potential method to reduce the risk of transmission of virus by artificial insemination. In contrast, no changes in onset, level, and duration of viremia, and shedding of virus in semen were observed using the inactivated virus vaccine.
Meng X-J. Heterogeneity of PRRS virus; implications of current vaccine efficacy and future vaccine development. Vet Microbiol. 2000;74:309-329.
Martelli P, Cavirani S, Lavazza A (eds). 4th International Symposium on Emerging and Re-Emerging Pig Diseases: PRRS PMWS Swine Influenza. Palazzo Dei Congressi Rome, University of Parma, Parus, 2003.
Prieto C, Castro JM. PRRS in the boar; a review. Theriogeniology. 2005;63:1-16.
1 Wensvoort G, et al. Vet Quart. 1991;13:121.
2 Terpstra C, et al. Vet Quart. 1991;13:131.
3 Collins JE, et al. J Vet Diag Invest. 1992;4:117.
4 Benfield DA, et al. J Vet Diag Invest. 1992;4:127.
5 Murtaugh MP, et al. Proc 23rd Ann Leman Conf Minn. 1996;23:89.
6 Murtaugh MP, et al. Proc 24th Ann Leman Conf Minn. 1997;24:146.
7 Nelson EA, et al. J Clin Microbiol. 1993;31:3184.
8 Forsberg R, et al. Virol. 2002;299:38.
9 Plagemann PGW, et al. Emerg Infect Dis. 2003;9:903.
10 Forsberg R, et al. Virol. 2001;289:174.
11 Nelson CJ, et al. J Virol. 1999;73:270.
12 Stadejek T, et al. J Gen Virol. 2002;83:1861.
13 Vugt JJFA, et al. J Gen Virol. 2001;82:2615.
14 Mardassi H, et al. Can J Vet Res. 1994;58:55.
15 Christianson WT, Joo HS. Swine Health Prod. 1994:2.
16 Canon N, et al. Vet Rec. 1998;142:142.
17 Garner MG, et al. Aust Vet J. 1997;75:1997.
18 Done SH, et al. Br Vet J. 1996;152:153.
19 Yoon I. Swine Health Prod. 1993;1:5.
20 Cho SH, et al. J Vet Diagn Invest. 1993;5:259.
21 Dee SA, et al. Swine Health Prod. 1996;4:181.
22 Bierk MD, et al. Can J Vet Res. 2001;65:261.
23 Larochelle R, et al. Virus Res. 2003;96:3.
24 Johnson W, et al. Vet Immunol Immunopathol. 2004;102:233.
25 Baysinger AK, et al. Swine Health Prod. 1997;5:173.
26 Mortensen S, et al. Prev Vet Med. 2002;53:83.
27 Meier WA, et al. Virol. 2003;309:18.
28 Mengeling WL, et al. Vet Microbiol. 2003;93:13.
29 Lager KM, et al. Can J Vet Res. 2003;67:121.
30 Nelson EA, et al. J Vet Diagn Invest. 1994;6:410.
31 Albina E, et al. Vet Rec. 1994;134:567.
32 Yoon K-J, et al. J Vet Diagn Invest. 1995;7:305.
33 Zuckermann FA, et al. Adv Vet Med. 1999;41:447.
34 Molitor TW, et al. Vet Microbiol. 1997;55:265.
35 Shibata I, et al. J Vet Med. 2000;62:105.
36 Zimmerman JJ, et al. Vet Microbiol. 1997;55:187.
37 Lager KM, et al. Vet Microbiol. 1997;58:127.
38 Lager KM, et al. Vet Microbiol. 1997;58:113.
39 Houben S, et al. J Vet Med Series B. 1995;42:209.
40 Chung W-B, et al. Can J Vet Res. 1997;61:292.
41 Nodelijk G, et al. Vet Microbiol. 1997;56:21.
42 Dee SA, et al. Can J Vet Res. 2003;67:12.
43 Magar R, et al. Can J Vet Res. 1995;61:69.
44 Yoon K-J, et al. Vet Res. 1998;30:629.
45 Katz JB, et al. Vet Microbiol. 1995;44:65.
46 Larochelle R, Magar R. J Virol Meth. 1997;68:161.
47 Meng X-J, et al. J Gen Virol. 1995;76:3181.
48 Dee SA, et al. Can J Vet Res. 2001;65:254.
49 Yoon K-J, et al. J Vet Diagn Invest. 1995;7:386.
50 Key KF, et al. Vet Microbiol. 2001;83:249.
51 Stadejek T, et al. Med Wet. 2005;61:321.
52 Mengeling WL, et al. Am J Vet Res. 1996;57:834.
53 Halibur PG, et al. Vet Pathol. 1995;32:648.
54 Halibur PG, et al. J Vet Diag Invest. 1996;8:11.
55 Halibur PG, et al. Vet Pathol. 1996;33:159.
56 Yaeger MJ, et al. Swine Health Prod. 1993;1:7.
57 Halbur PG, et al. J Clin Microbiol. 2000;38:1156.
58 Galina L, et al. Vet Rec. 1994;134:60.
59 Thanawongnuwech R, et al. Vet Path. 2000;37:143.
60 Feng WH, et al. J Virol. 2001;75:4889.
61 Wills RW, et al. Vet Microbiol. 2000;71:177.
62 Brockmeier SL, et al. Am J Vet Res. 2000;61:892.
63 Thacker EL, et al. Vaccine. 2000;18:1244.
64 van Alstine WG, et al. Vet Microbiol. 1996;49:297.
65 Dee SA. Swine Hlth Prod. 1996;4:147.
66 Dee SA. Proc Am Ass Swine Pract. 1997:465.
67 Thacker EL, et al. J Clin Microbiol. 1999;37:620.
68 Zeman DH. Swine Health Prod. 1996;4:143.
69 Dee S, et al. Proc Am Ass Swine Pract. 2001;32:191.
70 Mengeling WL. Proc 4th Int Symp Emerg Re-emerg Pig Dis 2003; p. 3.
71 Rossow KD, et al. Vet Rec. 1999;144:444.
72 Rossow KD, et al. Vet Path. 1995;32:361.
73 Chang CG, et al. J Virol. 2000;76:4750.
74 Zimmermann JJ, et al. Swine Hlth Prod. 1997;5:74.
75 Horter DC, et al. Vet Microbiol. 2002;86:213.
76 Wills RW, et al. J Clin Microbiol. 2003;41:58.
77 Van Reeth K, et al. Danske Vet. 2002;85:6.
78 Bierk MD, et al. J Vet Diag Invest. 2005;13:165.
79 Wagstrom EA, et al. Am J Vet Res. 2001;62:1876.
80 Rossow KD, et al. J Vet Diag Invest. 1994;6:3.
81 Wills RW, et al. Vet Microbiol. 1997;57:69.
82 Bilodeau R, et al. Can J Vet Res. 1994;58:291.
83 Stevenson GW, et al. J Am Vet Med Assoc. 1994:204.
84 Wills R, et al. J Swine Hlth Prod. 2002;10:161.
85 Cuartero L, et al. J Swine Hlth Prod. 2002;10:119.
86 Goldberg TL, et al. J Gen Virol. 2000;81:171.
87 Christopher-Hennings J, et al. J Vet Diag Invest. 2001;13:133.
88 Swenson SL, et al. J Am Vet Med Assoc. 1994;204:1943.
89 Christopher-Hennings J, et al. J Vet Diag Invest. 1995;7:456.
90 Solano GJ, et al. Vet Microbiol. 1997;55:247.
91 Gradil C, et al. Vet Rec. 1996;138:521.
92 Christopher-Hennings J, et al. Am J Vet Res. 1997;58:40.
93 Batista L, et al. J Swine Hlth Prod. 2002;10:147.
94 Mengeling WL, et al. Am J Vet Res. 1998;59:52.
95 Rowland RRR, et al. Vet Microbiol. 2003;96:219.
96 Botner A, et al. Vet Rec. 1997;141:497.
97 Otake SA, et al. Vet Rec. 2002;150:804.
98 Mengeling WL. J Swine Hlth Prod. 2005;13:910.
99 Otake SA, et al. J Swine Hlth Prod. 2002;10:59.
100 Otake S, et al. Vet Rec. 2002;150:102.
101 Amass SF, et al. Swine Hlth Prod. 2000;8:161.
102 Otake SA, et al. Can J Vet Res. 2003;67:265.
103 Otake SA, et al. Vet Rec. 2003;152:73.
104 Otake S, et al. Can J Vet Res. 2003;67:198.
105 Otake S, et al. Vet Rec. 2004;154:80.
106 Wills RW, et al. Swine Hlth Prod. 1995;5:213.
107 Torremorrell M, et al. Am J Vet Res. 1997;58:828.
108 Dee SA, et al. Vet Rec. 2005;156:56.
109 Le Potier MF, et al. Vet Microbiol. 1997;55:355.
110 Hooper CC, et al. J Vet Diag Invest. 1994;6:13.
111 Pirtle EC, Beran GW. J Am Vet Med Assoc. 1996;208:390.
112 Dee SA, et al. Vet Rec. 2005;156:56.
113 Larochelle R, Magar R. Vet Microbiol. 1997;58:1.
114 Main RG. Proc 11th Ann Iowa Swine Dis Conf 2003; p. 172.
115 Nielsen J, et al. Vet Immunol Immunopathol. 2003;93:135.
116 Riber U, et al. Vet Immunol Immunopathol. 2004;99:169.
117 Kawashima K, et al. Vet Immunol Immunopathol. 1999;71:257.
118 Lamontage L, et al. Vet Immunol Immunopathol. 2001;82:65.
119 Nielsen H-S, et al. J Virol. 2003;77:3702.
120 Aasted B, et al. Clin Diag Lab Immunol. 2002;9:1229.
121 Feng WH, et al. Vet Immunol Immunopathol. 2003;94:35.
122 Johnsen CK, et al. Viral Immunol. 2002;15:549.
123 Wills RW, et al. J Clin Microbiol. 2003;41:58.
124 Beyer J, et al. J Vet Med Sci B. 2000;47:9.
125 Rowland RR, et al. Vet Microbiol. 2003;96:219.
126 Delpuite PL, et al. Arch Virol. 2002;76:4312.
127 Nauwynck HJ, et al. J Gen Virol. 1999;80:297.
128 Chou MT, et al. Vet Microbiol. 2000;71:9.
129 Choi C, Chae C. J Comp Path. 2002;127:106.
130 Labarque G, et al. Vet Res. 2003;34:249.
131 Miller LC. Arch Virol. 2004;149:2453.
132 Yoon K-J, et al. Vet Res. 1999;30:629.
133 Kreutz LZ, Ackermann MR. Virus Res. 1996;42:137.
134 Duan X, et al. J Virol. 1998;72:4250.
135 Yoon K-J, et al. Vet Immunol. 1996;9:51.
136 Rossow KD, et al. Vet Pathol. 1995;32:361.
137 Wissink EHJ, et al. Arch Virol. 2003;148:177.
138 Oleksiewicz SD, Nielsen T. Vet Microbiol. 1999;66:15.
139 Sirinarumitr T, et al. J Gen Virol. 1998;79:2989.
140 Thanawongnuwech R, et al. Vet Immunol Immunopathol. 2003;91:73.
141 Bautista EM, Molitor TW. Arch Virol. 1999;76:4312.
142 Chung HK, Chae C. J Comp Path. 2003;129:205.
143 Suradhat S, et al. J Gen Virol. 2003;84:453.
144 Lopez Fuertes L, et al. Virus Res. 2001;69:41.
145 Lopez Fuertes L, et al. Virus Res. 1999;64:33.
146 Albina E, et al. Vet Immunol Immunopathol. 1998;61:49.
147 Segales J, et al. J Comp Path. 1998;118:231.
148 Feng WH, et al. Proc 16th Int Pig Vet Soc Cong 2000; p. 657.
149 Cooper VL, et al. J Vet Diag Invest. 1997;9:198.
150 Rossow KD, et al. J Vet Diag Invest. 1994;6:3.
151 Sur J-H, et al. Vet Path. 1997;35:506.
152 Sur JH, et al. Vet Path. 2001;38:58.
153 Park BK, et al. Am J Vet Res. 1996;57:320.
154 Christianson WT, et al. Am J Vet Res. 1992;53:485.
155 Lager KM, Halibur PG. J Vet Diag Invest. 1996;8:275.
156 Lager KM, Ackermann MR. J Vet Diag Invest. 1994;6:480.
157 Benson JE, et al. Swine Hlth Prod. 2000;8:155.
158 Christianson WT, et al. Can J Vet Res. 1993;57:262.
159 Cheon DS, Chae C. Arch Virol. 2000;45:1481.
160 Mengeling WL, et al. Am J Vet Res. 1994;55:1391.
161 Lager KM, Mengeling WL. Am J Vet Res. 1995;59:187.
162 Lager KM, et al. Vet Rec. 1996;138:227.
163 Benson JE, et al. Theriogen. 2001;56:777.
164 Miller LC, Fox JM. Vet Immunol Immunopathol. 2004;102:131.
165 Kim TS, et al. Virus Res. 2002;85:133.
166 Drolet R, et al. Vet Path. 2003;40:143.
167 Goldberg TL, et al. Prev Vet Med. 2000;43:293.
168 Allan GM, et al. Arch Virol. 2000;145:2421.
169 Harms PA. Vet Path. 2001;38:528.
170 Rovira A, et al. J Virol. 2002;76:3232.
171 Thacker EL, et al. Vaccine. 2000;18:1244.
172 Brockmeier S, et al. Am J Vet Res. 2000;62:521.
173 Brockmeier SL, Lager KM. Vet Microbiol. 2002;89:267.
174 Solano GL, et al. Can J Vet Res. 1998;62:251.
175 Segales J, et al. Vet Microbiol. 2002;85:23.
176 Yoon K-J, et al. Vet Med. 1996;91:779.
177 Wills RW, et al. Vet Microbiol. 2000;71:177.
178 Halbur P, et al. J Clin Microbiol. 2000;38:1156.
179 Thanawongnuwech R, et al. Vet Path. 2000;37:143.
180 Labarque G, et al. Vet Microbiol. 2002;88:1.
181 Gucht S, et al. J Clin Microbiol. 2003;41:960.
182 Thanawongnuwech R, et al. Clin Diag Virol. 2004;11:901.
183 Prieto C, et al. Theriogeniology. 2003;60:1505.
184 Done SH, et al. Pig J. 2005;55:230.
185 Dee SA, Joo HS. J Am Vet Med Assoc. 1994;205:1017.
186 Baysinger AK, et al. Swine Health Prod. 1997;5:179.
187 Meier W, et al. Proc Am Ass Swine Pract. 2000:415.
188 Samsom JN, et al. J Gen Virol. 2000;81:497.
189 Asai T, et al. Vet Microbiol. 1999;70:143-148.
190 Halbur PG, et al. Vet Rec. 2002;151:344.
191 Botner A. Vet Microbiol. 1997;55:295.
192 Mengeling WL, et al. J Vet Diag Invest. 1995;7:3.
193 Mengeling WL, et al. J Vet Diag Invest. 1996;8:238.
194 Christopher-Hennings J, et al. J Clin Microbiol. 1995;33:1730.
195 Dee SA, Philip RE. Swine Hlth Prod. 1999;7:237.
196 Donadeu M, et al. Swine Hlth Prod. 1999;7:255.
197 Cheon DS, Chae C. Arch Virol. 2000;145:1481.
198 Legeay O, et al. J Virol Meth. 1997;68:65.
199 Chung H-K, et al. J Vet Diag Invest. 2002;14:56.
200 Umthun AR, Mengeling WL. Am J Vet Res. 1999;60:802.
201 Vincent A, Thacker E. Proc A Ass Swine Vet. 2001;31:15.
202 Egli C, et al. J Virol Meth. 2001;98:63.
203 Botner A, et al. Vet Microbiol. 1999;68:187.
204 Halibur PG, et al. Vet Pathol. 1995;32:200.
205 Takashima H, Tominatsu H. J Jap Vet Med Ass. 1999;52:772.
206 Larochelle R, Magar R. J Vet Diag Invest. 1995;7:540.
207 Larochelle R, et al. Can Vet J. 1994;35:513.
208 Sirinarumitr T, et al. J Vet Diag Invest. 2001;13:68.
209 Kleiboeker SB, et al. J Vet Diag Invest. 2005;17:165.
210 Cho H-J, et al. Can J Vet Res. 1997;61:161.
211 Sorensen KJ, et al. Vet Microbiol. 1998;60:169.
212 Cho HJ, et al. Can J Vet Res. 1997;61:299.
213 Mortensen S, et al. Danske Vet. 1999;82:626.
214 Mortensen S, et al. Vet Res. 2001;32:441.
215 Park BK, et al. J Vet Diag Invest. 1995;7:544.
216 Yoon IJ, et al. J Vet Diag Invest. 1994;6:289.
217 Christianson WJ, Joo HS. Swine Hlth Prod. 1994;2:10.
218 Paton DJ, Drew TW. Vet Rec. 1995;136:297.
219 Halbur PG, et al. Vet Path. 1995;32:648.
220 Halbur PG, et al. Proc Am Ass Swine Pract. 2000:319.
221 Thanawongnuwech R, et al. Vet Immunol Immunopathol. 1997;59:323.
222 Kranker S, et al. Vet Microbiol. 1998;61:21.
223 Sur JH, et al. Vet Path. 1998;35:506.
224 Rossow KD. Vet Pathol. 1998;35:1.
225 Feng WH, et al. J Virol. 2001;75:4889.
226 Larochelle R, Magar R. J Virol Meth. 1997;63:227.
227 Thanawongnuech R, et al. J Vet Diag Invest. 1997;9:334.
228 Uchinuno Y, et al. J Jap Vet Med Ass. 1998;51:713.
229 Yaeger M, et al. J Vet Diag Invest. 2002;14:15.
230 Fano E, et al. Can J Vet Res. 2005;69:71.
231 Dee S, et al. Can J Vet Res. 2001;65:22.
232 Dee S, et al. Can J Vet Res. 2005;69:58.
233 Dee SA, et al. Vet Rec. 1997;140:247.
234 Dee SA, Joo HS. Vet Rec. 1994;135:6.
235 Dee S, et al. Swine Health Prod. 1995;3:64.
236 Torremorell M, et al. J Swine Hlth Prod. 2002;10:153.
237 Bautista L, et al. J Swine Hlth Prod. 2002;10:147.
238 McCaw MB, et al. Swine Hlth Prod. 2000;8:15.
239 Desrosiers R, Boutin M. J Swine Hlth Prod. 2002;10:23.
240 Dee SA, et al. Can J Vet Res. 2005;69:64.
241 Bouwkamp FT. Tijd Diergeneesk. 1999;124:530.
242 Mengeling WL, et al. Am J Vet Res. 1999;60:796.
243 Torrison J, et al. Proc Am Ass Swine Pract. 1996;27:89.
244 Shin J, et al. Vet Microbiol. 1997;55:337.
245 Vilaca KJ, et al. Proc Am Ass Swine Vet. 2001;32:59.
246 Mavromatis I, et al. J Vet Med B. 1999;46:603.
247 Dewey CE, et al. Prev Vet Med. 1999;40:233.
248 Mengeling WL, et al. Vet Microbiol. 2003;93:25.
249 Madsen KG, et al. Arch Virol. 1998;143:1683.
250 Storgaard T, et al. Arch Virol. 1999;144:2389.
251 Nielsen J, et al. J Gen Virol. 2001;82:1263.
252 Nielsen J, et al. Vet Microbiol. 2002;84:1.
253 Woensel van PAM. Vet Rec. 1998;142:510.
254 Hesse RA, et al. Proc Am Assoc Swine Pract. 1997:137.
255 Kwang J, et al. Res Vet Sci. 1999;67:199.
Enzootic in sub-Saharan Africa and Egypt and recently the Arabian peninsular. Virus maintained in flood water mosquitoes and transmitted by hematophagous insects. Ruminants are amplifying hosts. Epizootics in high rainfall periods
Rift Valley fever virus, a member of the family Bunyaviridae, genus Phlebovirus. Isolates from outbreaks in different countries are antigenically similar and there is only minor genetic variation between isolates.1,2
Rift Valley fever was initially reported in the Rift Valley in Kenya but now exists and occurs as epizootics throughout sub-Saharan Africa with recent extensions into Egypt and Madagascar, Mauritania and most recently expansion to the Arabian peninsula.3,4 It has great potential for spread to other countries. The pattern of occurrence is cyclical epidemics with periods of quiescence between, with the majority of cattle in enzootic areas remaining seronegative for periods of 5 years. A Rift Valley fever-like disease is reported in sheep in India.
The virus is believed to be maintained through a cycle involving mosquito vectors, wildlife and domestic livestock and by transovarial transmission in certain floodwater Aedes mosquitoes which have drought-resistant eggs that survive several years without hatching. These interepizootic vectors belong to the Aedes subgenus Neomelaniconion in East Africa and the subgenus Aedimorphus in West Africa.5 Epizootics occur in enzootic areas when wet and flood conditions promote the expansion of the vector population in the presence of susceptible livestock. Ruminants are highly susceptible and serve as the main amplifying hosts.5 A pronounced, but short, viremia occurs in infected animals and facilitates the spread of the disease by biting insects. Virus is also present in milk, feces and aborted fetuses. An unidentified wildlife reservoir host may also exist.
A wide variety of mosquitoes from several genera have been identified as vectors, or possible vectors, including species on continents such as Australia and North America. Sandflies and culicoides have also been identified as vectors but are not maintenance hosts.2,5,6
The disease can be transmitted by most routes including inoculation and the inhalation of aerosols. Following inoculation of sheep and cattle the incubation period is 1 to 2 days and high virus titers are found in blood. Virus persists in the body for approximately 3 weeks but long-term carriage has not been observed. Pregnant animal abort but infection may be clinically mild in non-pregnant animals. IgM antibody can be detected as early as 4 days after infection and persists for 2 to 6 months.2,7-9
The incidence of the disease varies with the size of the vector population. It is greatest in seasons of heavy rainfall which allows the vector population to increase and expand from permanent water sites to breed in surface waters in normally dry areas.10,11 Expanding irrigation schemes may also enlarge areas at risk.
Losses are due mainly to deaths in young lambs and calves, although there may be a high incidence of abortions and some deaths in adult sheep and cattle.
Mortality is higher in lambs than in calves. Indigenous breeds may have inapparent infections. Camels, domestic buffalo, monkeys, humans, mice, rats, ferrets, and hamsters are susceptible to infection and goats moderately so, but pigs, rabbits, guinea pigs, and poultry are not. A large number of different African wildlife species also have seropositivity in endemic areas.12,13 Trade animals are suspect as the source of infection to previously free areas.
The disease in humans is usually a transient illness but complications of hemorrhagic fever, retinal disease and encephalitis occur. Traditionally the groups exposed to greatest risk are laboratory workers handling the virus and those working amongst infected animals or their products, including veterinarians. However cases were not limited to these groups in the large outbreaks in Egypt in 1977 and 1978 and the more recent outbreaks in the Arabian peninsular and the occurrence rate in humans was very high in Egypt (more than 20 000 cases in 1977 with 600 deaths). In Saudi Arabia the case fatality was 14% in one cohort of 886 human cases.14 The agent is identified as one for potential bioterrorism.15
Hepatocytes are the primary site of viral replication in lambs and calves and age is a determining factor in the progression and outcome of infection.16,17 In very young animals, hepatic lesions progress from degeneration and necrosis of individual hepatocytes to extensive necrosis throughout the liver resulting in hepatic insufficiency and failure. In young animals, encephalomyelitis may also occur.16
The major presentation is a regional outbreak of abortion and neonatal mortality. In lambs and calves, after an incubation period of about 12 h there is a sudden onset of high fever and incoordination followed by collapse and death within 36 h in 95–100% of affected lambs and 70% of young calves.
In adult sheep and cattle, abortion is the outstanding sign but the mortality rate in adult sheep may be as high as 20–30% and 10% in cattle. In less severe cases in cattle there is febrile disease and dysgalactia and some animals develop emaciation with jaundice. In fatal cases, sudden death is preceded by a high fever for 1–2 d. Goats show a febrile reaction but few other clinical signs.
Severe leukopenia is a common finding. Antibodies appear in the serum about 1 week after infection and persistence depends on antibody type. Sera are usually screened using hemagglutination-nhibition or ELISA tests and positives confirmed with plaque reduction neutralization tests.13,18 Transmission tests to white Swiss mice and sheep are also used.
ELISA tests that meet the desire for an accurate and safe test and that use inactivated antigen and that can meet international validation requirements are described.19,20
Extensive hepatic necrosis is the characteristic lesion in Rift Valley fever. Other non-specific lesions include congestion and petechiation in the heart, lymph nodes, gallbladder, and alimentary tract. Abomasal and intestinal content may be dark brown to red due to hemorrhage. Microscopically there is focal or diffuse necrosis of the liver and there may be acidophilic intranuclear inclusion bodies in hepatic cells. The lesions are much more extensive in newborn lambs and calves than in older animals.16,17,21 Immunohistochemical localization of viral antigens in tissues provides a specific diagnosis.22
Note the zoonotic potential of this disease when handling these specimens.
In regions where this disease has not occurred it should be suspect when there is an area outbreak of abortion and neonatal mortality in sheep and cattle coupled with an area outbreak of flu-like disease in humans
• Brodifacoum poisoning has been mistaken for Rift Valley fever.21
Little attention has been given to the aspect of treatment of the disease and no known treatment is of any value.
Vector control and quarantine may aid in protection of livestock and humans in enzootic areas but vaccination is the single most practical and economic control measure. Killed-virus and living attenuated virus vaccines are available.
Live attenuated vaccines and mutagenized live virus vaccines provide good protection which lasts for at least 28 months but are not recommended for pregnant animals because they are abortigenic, causing fetal death and some teratogenic anomalies. The recorded problems include hydrops amnii, arthrogryposis, hydranencephaly, and microencephaly. There is also a concern for reversion to virulence.
Killed-virus vaccines require repeat administration for good immunity and annual vaccination of all dairy cattle is recommended as a cost-effective control program in endemic countries. They are also recommended for pregnant and young animals.
A mutagen attenuated vaccine protects against challenge in both sheep and cattle.23,24 Viremia following vaccination is minimal and thought not to be a risk for infection of susceptible mosquitoes.24 Mutagenic vaccines were initially thought to have no deleterious effect on the fetus but abortion and teratogenicity has been observed in the lambs of sheep vaccinated early in pregnancy.25
Prevention of the introduction of Rift Valley fever into countries free of the disease requires the prohibition of the importation of all susceptible species from Africa. All necessary steps to prevent the introduction of infective insects and infected biological materials should be taken. The possibility of humans carrying the infection from country to country is very real.
1 Rollin PE, et al. Emerg Infect Dis. 2002;8:1415.
2 Worthington RW, Bigalke RD. Am J Vet Res. 2001;68:291.
3 Madani TA, et al. Clin Infect Dis. 2003;37:1084.
4 Paweska JT, et al. Onderstepoort J Vet Res. 2003;70:49.
5 Zeller HG, et al. Am J Trop Med Hyg. 1997;56:265.
6 Mellor PS, et al. Ann Rev Entomol. 2000;45:307.
7 Morrill JC, et al. Am J Vet Res. 1997;58:1110.
8 Morvan J, et al. Trans Roy Soc Trop Med Hyg. 1992;86:675.
9 Peters CJ, et al. Res Virol. 1989;140:43.
10 Bicout DJ, Sabatier P. Vector Borne Zoonot Dis. 2004;4:33.
11 Davies FG, et al. Epidemiol Infect. 1992;108:185.
12 House C, et al. Ann NY Acad Sci. 1996;791:345.
13 Olaleye OD, et al. Rev Sci Tech Off Int Epiz. 1996;15:937.
14 Madani TA, et al. Clin Infect Dis. 2003;37:1084.
15 Sidwell RW, Smee DF. Antiviral Res. 2003;57:101.
16 Rippy MK, et al. Vet Pathol. 1992;29:495.
17 Van Der Lugt JJ, et al. Onderstepoort J Vet Res. 1996;63:341.
18 Meegan JM, et al. Am J Vet Res. 1987;48:1138.
19 Paweska JT, et al. Onderstepoort J Vet Res. 2003;70:49.
20 Paweska JT, et al. J Virol Methods. 2003;113:103.
21 Coetzer JAW. Onderstepoort J Vet Res. 1982;49:11.
22 Rippy MK, et al. Vet Pathol. 1992;29:495.
23 Hubbard KA, et al. Am J Vet Res. 1991;52:50.
Akabane virus in the Simbu serogroup of Bunyavirus: Cache Valley virus in the Bunyamwera serogroup of Bunyavirus
Transmission by hematophagous insects. Outbreaks when cattle or sheep are infected in early pregnancy.
Abortions, stillbirths and birth of calves with skeletal deformities and neurological disorders.
Akabane virus and Cache valley viruses are both members of the genus Bunyavirus in the family Bunyaviridae with Akabane virus a member of the Simbu serogroup of the genus Bunyavirus and Cache Valley virus a member of the Bunyamwera serogroup of the genus Bunyavirus. There are a large number of members of the Bunyavirus genus and several can produce clinically inapparent infections in ruminants but Akabane virus and Cache Valley virus produce fetal disease when they infect the dam in early pregnancy.1-3 There are subtypes of these viruses.4
Other Bunyavirus that have been associated with natural or experimentally produced fetal disease in ruminants include:
• Simbu serogroup. Aino and Peaton viruses2,5,8
• Bunyamwera serogroup. Main Drain viruses6,7
• California serogroup. LaCrosse and San Angelo viruses.7
Antibodies to the related, but as far as is known non-pathogenic, viruses Douglas and Tinaroo have been detected in cattle, sheep, goat, buffalo and deer.1,2
Serologic studies suggest that infection occurs in cattle, sheep, goats, horses, donkeys, camels, pigs, and buffaloes but disease occurs only in calves, lambs, and goat kids.9
The disease is most common in calves and has been recorded as the cause of epizootics of abortion, stillbirths and congenital malformation in calves in Australia, Israel, Iran, Kenya, Japan, Korea, and Taiwan with high attack rates in affected herds. Congenital disease in lambs is less common but is recorded in Israel and Australia.5 The virus has also been isolated from insect vectors in Africa and is the probable cause of the ‘rigid lamb syndrome’ in Zimbabwe. Serological surveys suggest widespread distribution of the virus in the Middle East, Asia and southeast Asia, and in parts of Africa.2,10,11 Whereas infection in adult cattle is common in endemic areas, reports of clinical disease are rare but neurological disease associated with infection in cattle 2 to 7 years of age has been observed.12
There is serologic evidence that infection occurs in sheep, goats, horses, cattle, pigs and in several wildlife species but disease is recorded only in sheep. The disease in sheep is recorded as an occasional epizootic in flocks in North America.4,7,13 Cache Valley virus is one of the more common Bunyaviruses in North America and has been isolated from mosquito pools collected in 22 states and several provinces in Canada and Mexico and also in Central and South America.4,7
The viruses are maintained through a cycle involving vectors, in which there is probably transovarial transmission, and a susceptible vertebrate population. Replication occurs in both vertebrate and insect populations.
Viremia in cattle is short-lived, lasting 1–9 d and long-term carriers are not believed to occur. Herbivores appear essential to the vector–virus–host cycle16 and there is serological evidence of infection in cattle, sheep, goats, camels, horses, and buffaloes.2,15,17
In Australia, transmission is by the bites of Culicoides brevitarsis and C. nebeculosus.18 Virus has been isolated from C. brevitarsis and this is probably the major vector as serological data in Australia shows that most identified infections are within the known habitat of C. brevitarsis. Introduction of the virus into the bovine uterus in semen causes no developmental defects.
The vector(s) for Akabane disease in Japan and Korea are C. brevitarsis, Culicoides oxystoma and Aedes vexans and Culex tritaeniorhynchus.3,9
The virus has been isolated from mosquitoes and Culicoides spp.4,7 Mosquitoes are the believed vector but the species involved and the natural history of the disease are not known.
The virus has been isolated from mosquitoes and midges including C. brevitarsis.2 Serological studies show antibody in cattle, sheep, goats, and buffalo but not camels, dogs or horses.
The seasonal and geographic pattern of epizootics of abortions and premature births are determined by the distribution of vectors and the availability of susceptible ruminant populations in early pregnancy.
In the north of Australia, C. brevitarsis is active throughout the year and cattle are infected with Akabane virus before their first pregnancy and disease does not occur. Epizootics occur in southern Australia when C. brevitarsis extends its range of distribution,19 probably by wind-borne spread from the north, to infect immunologically naive herds. Abortions and premature births commence in the autumn, with clinical cases of arthrogryposis, and hydranencephaly occurring in mid-winter.
Wind-borne introduction of Culicoides spp. is also postulated as the means of introduction of infection in Israel.20 The movement of immunologically naive pregnant cattle into an enzootic area can be the result in severe outbreaks in those herds.21
The disease is likely to disappear for intervals of 5–10 years, until there is combination of a susceptible population and a heavy vector population. Occurrences of the disease are also dependent on the presence of susceptible, early pregnant females at the time that the vectors are plentiful. These conditions are provided by a series of years of drought in an enzootic area, so that there are no insect vectors, no infection, and no immunization activity of prepubescent females, followed by a wet season when the vectors are plentiful.
Outbreaks occur after a long period of drought and winter frosts reducing the population of mosquito vectors and resulting in populations of seronegative ewes. Mating in the summer appears a major risk factor allowing sheep to be in the susceptible stage of pregnancy during the vector season.22 Many outbreaks are in areas that interface between suburban and rural environments.7
Viremia occurs in the dam for 2–4 d, with an antibody peak 4–5 d after the viremia and a subsequent secondary rise. The dam is unaffected but there is a focal viral persistence in cotyledons and subsequent viremia in the fetus.
Inflammatory and degenerative lesions occur in the central nervous system but tissue tropism and damage is determined by the age of the fetus and its ability to mount an immune response. Three forms, or principal manifestations, of the disease in an affected herd are described. The first is arthrogryposis occurring in calves infected at an older age than others (fetus infected at 105–174 d of pregnancy). The second is arthrogryposis accompanied by hydranencephaly. The third is hydranecephaly only (infected between days 76 and 104 of pregnancy).
With arthrogryposis, there is almost complete absence of ventral horn cells in the spinal cord and an accompanying neurotropic failure of muscle development. Contracture of the joints results. The hydranencephaly is manifested by a partial or complete failure of development of the cerebral cortex. The brainstem and cerebellum are usually normal.
Several other manifestations have been described. They include pre-arthrogryposis groups of calves with incoordination and a mild to moderate non-suppurative encephalitis, and other calves with flaccid paralysis and active secondary demyelination in motor areas of the spinal cord. Some calves are unable to stand and have thickened dorsal cranial bones and hydranencephaly involving anterior and mid-brainstem, and a diminutive cerebellum. The infection with Akabane virus is also credited with causing abortion, stillbirth and premature birth.
Lesions produced in lambs by experimental inoculation of the ewes during early pregnancy (days 32–36) include skeletal muscle atrophy and degeneration, and inflammatory and degenerative lesions in the cerebrum; the lesions in the central nervous system vary from porencephaly to hydranencephaly. There are also brachygnathism, scoliosis, hypoplasia of the lungs, agenesis or hypoplasia of the spinal cord, and arthrogryposis.25 Lesions are also present in fetuses of ewes inoculated between 29 and 45 days of gestation.15
Ovine fetuses are susceptible to the teratogenic effects between 28 and 48 days of gestation.13 Destructive lesions occur in the central nervous system but infection of fetal membranes with a reduction in the volume of amniotic fluid and constriction by membranes around the fetus are believed to contribute to the occurrence of arthrogryposis.7
Infection in adult cattle is most commonly clinically inapparent, unless there is dystocia, but neurological disease manifest with hypersensitivity, tremor and ataxia is recorded.12 In calves, the two syndromes, arthrogryposis and hydranencephaly, occur separately; arthrogryposis in the early stages of the outbreak and hydranencephaly at the end. Calves with both defects occur in the middle of the outbreak. In some outbreaks only one of the manifestations of the disease is seen.26,27
Calves with arthrogryposis almost always are the subjects of difficult birth requiring physical assistance. They are small and significantly underweight but they are fully mature in terms of teeth eruption and hair coat and hoof development. They are unable to rise, stand or walk. One or more limbs is fixed at the joints: there is a congenital articular rigidity. The limb is usually fixed in flexion but it may be in extension. The joint becomes freely movable if the tendons around it are severed, that is, there is no abnormality of the articular surface. The muscles of affected limbs are severely wasted. Kyphosis or scoliosis are common.
Calves with hydranencephaly have no difficulty rising and walking. The major defects are a lack of intelligence and blindness. They will suck if put onto the teat but if this is not done, they stand and bleat and have no apparent dam-seeking reflex. A few calves have microencephaly and are more severely affected. They are dummies, very uncoordinated in gait, unable to stand properly and move erratically when stimulated. These calves appear at the very end of the outbreak.
As well as the skeletal and neurological diseases, cases of abortion, stillbirth and premature birth are also regarded as being associated with Akabane virus infection in cows. They are usually recorded at the beginning of the outbreak before the neurological defects occur.
The presence of specific antibody in fetal sera or the precolostral sera of neonates is diagnostic but its absence does not exclude the diagnosis if infection precedes the development of immunological competence. Precolostral sera from several animals should be tested and most cases are positive at high titer.2,24 A rising titer with paired samples from the dam, or a high titer in the serum of surviving neonates is suggestive of recent infection but not confirmatory for disease. Serological tests include microneutralization, hemagglutination inhibition, agar gel immunodiffusion (AGID) and an (ELISA) test.2,28,29
The primary lesions with both Akabane and Cache Valley infections in the fetus are a necrotizing non-suppurative encephalomyelitis and polymyositis.2
In calves and lambs with arthrogryposis there is severe muscle atrophy, fixation of joints by tendon contracture and normal articular surfaces. The joints are easily released by cutting the surrounding tendons. Histologically, there may be almost complete absence of ventral horn cells in the spinal cord. This lesion may be localized to one segment of the cord and viral antigen may be demonstrated via immunohistochemistry.25
In calves and lambs with hydranencephaly the cerebral hemispheres are completely absent and the vacant space is filled with fluid enclosed by the normal meninges. In a few cases the lesions will be limited to porencephaly. In most, the brainstem and cerebellum lack cavitations but diminution of their size may be recorded.
Akabane virus disease and Cache Valley virus disease in sheep, as they are manifest epidemiologically, are well-defined and easily recognizable entities. Differentials include:
• Lupine-induced arthrogryposis in calves
• Manganese deficiency in calves
• Heritable forms of arthrogryposis and/or micrencephaly
• Fetal infection with bluetongue virus, rift valley fever virus, or pestivirus
Cattle in Japan may also produce hydranencaphalic calves, which are recumbent, opisthotonic and unable to suckle at birth, when infected during pregnancy by the Chuzan virus.30,31 The virus, a member of the Polyam subgroup of orbiviruses, is transmitted by Culicoides oxystoma.
In Africa infection with flaviviruses including West Nile, Banzi and AR5189 also cause abortion, stillbirth and congenital brain malformations.32
No treatment would be contemplated because affected calves are not viable nor humanely kept alive.
Vector control is not possible with current knowledge and vaccination is the only effective method of control. Killed vaccines for Akabane virus have proved very effective against natural exposure and are available in Japan and Australia.2,15 They require two inoculations prior to pregnancy and an annual booster. The economics of their annual use is dictated by the risk of disease in regions subject to periodic outbreaks of disease.
Konno S, et al. Akabane disease in cattle: congenital abnormalities caused by viral infection. Spontaneous disease. Vet Pathol. 1982;19:246-266.
Charles JA. Akabane virus. Vet Clin North Am Food Anim Pract. 1994;10:525-546.
Edwards JF. Cache Valley virus. Vet Clin North Am Food Anim Pract. 1994;10:5515-5524.
de la Concha-Bermejillo A, et al. Cahe Valley virus is a cause of fetal malformation and pregnancy loss in sheep. Small Rumin Res. 2003;49:1-9.
1 Cybinski DH. Aust J Biol Sci. 1984;37:91.
2 Charles JA. Vet Clin North Am Food Anim Pract. 1994;10:525.
3 Stram Y, et al. Virus Res. 2004;104:93.
4 de la Concha-Bermejillo A, et al. Small Rumin Res. 2003;49:1.
5 Haughey KG, et al. Aust Vet J. 1988;65:136.
6 Edwards JF, et al. Am J Trop Med Hyg. 1997;56:171.
7 Edwards JF. Vet Clin North Am Food Anim Pract. 1994;10:515.
8 Tsuda T, et al. Vet Res. 2004;35:531.
9 Chin-Chen H, et al. Vet Microbiol. 2003;24:1.
10 Taylor WP, Mellor PS. Epidemiol Infect. 1994;113:175.
11 Mohamed MEH, et al. Rev Med Vet Pays Trop. 1996;49:285.
12 Lee JK, et al. Vet Pathol. 2002;39:269.
13 Chung SJ, et al. Am J Vet Res. 1990;51:1645.
14 Brenner J. J Israel Vet Med Assoc. 2004;59:7.
15 Kirkland PD, Barry RD. In: St George TD (ed). Arbovirus Research in Australia. Proc 4th Symposium, 1986; p. 229.
16 Parsonson IM, et al. Adv Virus Res. 1985;30:279.
17 Nakamura K, et al. J Jpn Vet Med Assoc. 1987;40:513.
18 Jennings M, Mellor PS. Vet Microbiol. 1989;21:125.
19 Bishop AL, et al. Aust Vet J. 1996;73:174.
20 Braverman Y, Chechik F. Rev Sci Tech Off Int Epizoot. 1996;15:1037.
21 Jagoe S, et al. Aust Vet J. 1993;70:56.
22 Shelton M, et al. Sheep Goat Res J. 1994;10:124.
23 Parsonson IM, et al. Vet Microbiol. 1981;6:197. 209
24 Kirkland PD, et al. Vet Rec. 1988;122:582.
25 Narita M, Kawashima K. Am J Vet Res. 1993;54:420.
26 Tateyama S, et al. Res Vet Sci. 1990;49:127.
27 Brenner J, et al. J Vet Med Sci. 2004;66:441.
28 Ide S, et al. Vet Microbiol. 1989;20:275.
29 Ungar-Waron H, et al. Trop Anim Hlth Prod. 1989;21:205.
30 Miura Y, et al. Jpn J Vet Sci. 1990;52:689.