Vesicular exanthema of swine is an acute, febrile, infectious disease of swine associated with a calici virus. At least 34 types of calicivirus have been recognized in the ocean1 and new outbreaks continue to occur.2 The relationship between these viruses and VES is a continual source of speculation.3 The virus isolated in 2000 from sea lions was shown to be infectious for swine.2 It is indistinguishable clinically from foot-and-mouth disease (FMD) in swine, vesicular stomatitis and swine vesicular disease. It has not been a problem for the pig industry for over 40 years.
The causative virus is a calicivirus and 13 antigenic strains have been isolated with some variation in virulence between strains. Even in one herd the virus isolated may have been antigenically different from others. At least 17 antigenic types have been isolated since 1972. Only pigs are susceptible although experimental transmission to horses can be effected with some strains. All ages and breeds of pigs are susceptible to infection. The initial outbreak in pigs was traced to the feeding of meat from sea mammals.
It was first diagnosed in Southern California in 1932. In 1952, it was diagnosed outside California and by 1953 had occurred in 42 states. However rigid control eradicated it by 1956 with particular importance being paid to garbage feeding control.
Except for isolated outbreaks in Hawaii and Iceland, the disease has occurred only in the United States. It is important because of its direct effect and because of its resemblance to FMD. Although vesicular exanthema is a mild disease with a low mortality rate (usually less than 5% although there may be many deaths in unweaned pigs) affected animals may suffer a severe loss of body weight and convalescence may require several weeks. Pregnant sows may abort and lactating sows may go dry with resultant heavy losses in baby pigs. The disease was eradicated from the United States in 1959, 27 years after its initial appearance.4
The sources of infection are infected live pigs and infective pork. Infected pigs excrete the virus in saliva and feces but not in the urine for 12 h before vesicles develop and for 1–5 d afterwards. Raw garbage containing infective pork scraps is the most common medium of spread from farm to farm. On infected premises the disease is spread by direct contact and, although the virus is resistant to environmental influences, spread by indirect means does not occur readily. Pigs frequently become infected, as evidenced by the development of immunity, without evidence of clinical disease. Ingestion of infected material is sufficient to produce infection.
The isolation from marine animals of an identical virus, which is capable of producing a disease identical to vesicular exanthema when inoculated into pigs, has led to the hypothesis that the primary reservoir for vesicular exanthema is in marine animals. Epizootics in pigs may have been initiated by the feeding of marine meat or garbage containing marine animal products.
The virus is resistant to environmental influences and persists in frozen and chilled meats. It is readily destroyed by several different commonly used disinfectants including sodium hypochlorite, sodium hydroxide and phenol. A good immunity develops after an attack and persists for about 20 months. There is no appreciable cross-immunity between the strains of the virus and a series of outbreaks, each associated with a different strain of the virus, may occur in the one herd of pigs.
A similar if not identical virus, San Miguel sea lion virus, has been isolated from sea lions and fur seals off the coast of California in the United States. It is physically, chemically and morphologically identical to the vesicular exanthema virus, although the same antigenic types have not been found. The virus produces an identical disease to vesicular exanthema when inoculated into pigs and appears to have a similar host range. The vesicular exanthema of swine virus is infective for the harp seal but the disease is inapparent and self-limiting. The intradermal inoculation of the vesicular exanthema of swine virus into otrarid (fur) seal pups will result in plaque-like lesions. Feeding swine the seal tissues from the inoculation experiments will result in seroconversion in swine which were fed tissues from seals infected with the vesicular exanthema of swine virus but not in those which were fed tissues from seals infected with the San Miguel sea lion virus. Antibody to this virus has also been detected in California gray whales and in feral swine inhabiting coastal areas.
As in other vesicular diseases there is a viremia, lasting for 72–84 h and commencing 48 h before vesication, with localization occurring in the buccal mucosa and the skin above the hooves. The intradermal inoculation of the vesicular exanthema of swine virus and the San Miguel sea lion virus into swine results in fluid-filled vesicles at the sites of inoculation in the snout, coronary band, and tongue. Lesions are usually limited to the non-haired portions of the integument and tongue. A mild viral encephalitis occurs in pigs inoculated with the swine virus and the sea lion virus can be recovered from the brain tissue of pigs infected with the virus.
The incubation period varies with the virulence of the causative strain of virus but is usually 1–3 d. Morbidity is always high but mortality is low There is an initial high fever (40.5–41°C; 105–106°F) followed by the development of vesicles in the mouth, on the snout, on the teats and udder and on the coronary skin, the sole, the heel bulbs and between the claws, and accompanied by extreme lassitude and complete anorexia. The initial lesion is a blanched area which soon develops into a vesicle full of clear fluid. The vesicles rupture easily leaving raw, eroded areas. This usually occurs about 24–48 h after they appear and is accompanied by a rapid fall of temperature. Secondary crops of vesicles often follow and may cause local swelling of the face and tongue. Lesions on the feet may predominate in some outbreaks whereas in others they may be of little significance. The affected feet are very sensitive and there is severe lameness. Healing of the oral vesicles occurs rapidly although secondary bacterial infection often exacerbates the lesions on the feet. Recovery in uncomplicated cases is usually complete in 1–2 weeks. It may occasionally cause encephalitis, myocarditis, and diarrhea and failure to thrive. When sows become infected late in pregnancy, abortion frequently occurs and lactating sows may go dry.
Fluid from the vesicles is used in transmission experiments and for tissue culture. Blood serum is used for the complement fixation, viral neutralization in cell culture and gel diffusion precipitin tests.
Postmortem examinations are not of much value in the diagnosis of vesicular exanthema but the pathology of the disease has been defined. The lesions are limited to epithelial lesions where there are vesicles, necrosis, sloughing and rapid healing with mild scarring. Diagnosis involves virus isolation in cell culture, with electron microscopy as a possibility and various serologic tests including fluorescent antibody tests for the antigen. PCR tests have also been developed.
There is no effective treatment. The immunity is solid following infection but heterologous infection is possible.
Eradication of the disease should be attempted whenever practicable. In most instances it is essential to report to the regulatory authorities The first step is to quarantine infected premises and restrict movement of pigs in the area. Infected animals should be slaughtered but the carcasses may be salvaged for human consumption provided the meat undergoes special treatment to insure destruction of the virus. Normal freezing and chilling procedures are not sufficient to destroy it. All garbage fed to pigs must be boiled. Infected premises should be thoroughly cleaned and disinfected with a 2% sodium hydroxide solution before restocking. The implementation of these measures was eminently successful in eradicating the disease from the United States.
In view of the reservoir of virus in marine animals and apparent infection in feral swine in the coastal areas of California, it is possible that the disease could recur in domestic swine in the United States. Possible methods of reintroduction that need to be guarded against have been described.
Active immunization may be practicable if the disease reappears and other control measures fail. A formalin-killed virus preparation produces an immunity lasting for at least 6 months. Multivalent vaccines may be required if more than one strain of the virus is involved.
Recently the pathogenic class of VESV-like caliciviruses (genus vesivirus) endemic in certain ocean species and US livestock has possibly caused vesicular disease on the hands and feet of humans.5
Affects ruminants, rarely swine. Outbreaks in Asia, Middle East and tropical Africa, highly contagious and high mortality
Inhaled/ingested virus → upper respiratory infection → viremia → target cells (lymphocytes and alimentary mucosa) → signs and lesions
High fever, oculonasal discharge, salivation, ulcerative stomatitis, diarrhea, dehydration and death
Necrotic stomatitis and esophagitis, ulcerative and hemorrhagic enterocolitis, massive necrosis of lymphocytes in Peyer’s patches, lymph nodes and spleen
Rinderpest is associated with a morbillivirus (family Paramyxoviridae) and there are many strains with considerable variation in virulence between them but all are immunologically identical. Consequently, the immunity which develops after infection or vaccination with one strain protects against all other strains or isolates. Three genetically distinct lineages of the virus are now recognized, with lineages 1 and 2 being of African origin and lineage 3 of Asian origin,1 but the differences between lineages are small and do not affect the immunity induced.2 Rinderpest virus is quite fragile and is antigenically related to the other members of the morbillivirus group including the viruses causing peste des petits ruminants (PPR) in sheep and goats, canine distemper in dogs, measles in humans, phocine distemper in seals and hedgehog distemper.2
Historically, rinderpest (cattle plague) was a most devastating disease spread from Asia to Europe, the Middle East and Africa, usually as a sequel to wars. The need to combat the disease was instrumental in the establishment of the first veterinary school in 1762 in Lyon, France. Its complete eradication is the goal of the Global Rinderpest Eradication Program (GREP) of the Food and Agriculture Organization and the geographic distribution of the disease has been shrinking steadily since the beginning of the 20th century. Rinderpest was eradicated from southern Africa, Europe and China by the middle of that century. In the 1960s, the disease was cleared from West Africa and most of East Africa, but there was a dangerous resurgence less than 10 years later and again in the 1990s.
Most countries today claim to be free of rinderpest. At the end of the last century, the disease was still endemic in parts of Asia and in a small area bordering on Kenya and Somalia. In the 1980s, outbreaks occurred over much of tropical Africa and Asia. The most recent outbreaks occurred in Kenya and Tanzania (1993–97, 2003) and in Pakistan (2000–2002). The disease has never appeared in North America but there have been single outbreaks which were quickly eradicated in Brazil and Australia. All ruminants and pigs are susceptible to infection with rinderpest virus. Natural infection occurs commonly only in domestic cattle, buffalo and yak but in some outbreaks, sheep and goats do become infected and show clinical signs. European pigs are susceptible to infection but only show a mild transient fever and do not spread the disease. Pigs indigenous to Thailand and Malaysia are highly susceptible and natural spread of the clinical disease can occur. Similarly, clinical disease is common in Asian sheep and goats and they contribute to the persistence of the virus in the region. There is the belief that rinderpest became prevalent in small ruminants in Africa and Asia only after the introduction of goat-adapted rinderpest vaccine from which the virus of PPR probably mutated. One-humped camels become infected, but show no clinical signs.
Wildlife are often affected during outbreaks and the infection usually spreads to them from infected cattle. Nevertheless, it has been suggested that strains of the virus that are of low pathogenicity and low transmissibility could cycle in wildlife in the absence of disease in cattle. In the 1980–1983 outbreaks involving over 2 million cattle in Nigeria, free-living and captive wild animals also died but the disease did not occur in wildlife after it was eradicated from cattle.3 Similarly, wildlife (especially buffalo and eland) did not appear to act as reservoirs but as fully susceptible hosts during the Kenyan epidemic of 1993–1997 involving the lineage 2 virus in national parks.4 The wildlife most commonly affected are the buffalo, bushbuck, waterbuck and warthogs, all water and shade-loving. Others include the eland, giraffe, kudu, deer and wildebeest. An outbreak in the former Soviet Union involved yaks near the Mongolian border.3
In the absence of an outbreak, the prevalence of the disease in endemic countries is low. In India, it was less than 10 per 100 000 cattle before 1963, 5–7.5 per 100 000 in 1963–1974 and 2 per 100 000 in 1974–19885,6 as a result of great expansion of the numbers of vaccinated cattle. By mid-1990s, India was free of the disease. In general, recent vaccination campaigns in tropical Africa and Asia have greatly reduced the number of susceptible animals in the region, up to the point that one can say that the disease is currently under control worldwide.
When epidemics occur in highly susceptible populations, the morbidity and case–fatality rates approximate 100% and 50% (25–90%) respectively,7 and large numbers of in-contact animals may have to be destroyed. In endemic areas, most of the cattle population have some degree of immunity and case–fatality rates rarely exceed 30%. The African lineage 2 strain of the virus caused a high mortality in buffaloes but a milder form of the disease in transhumant cattle.8
Close contact between infected and non-infected animals is usually necessary for spread of the disease to occur because the virus does not survive for long outside the host. The virus is excreted by infected animals in urine, feces, nasal discharges, and perspiration. Transmission occurs through contaminated feed or by inhalation of aerosol. Survival of aerosolized virus depends particularly on humidity and it may last for more than 30 min at relatively low humidity. Ingestion of food contaminated by discharges of clinical cases, animals in the incubation stage, or animals with subclinical infections, may also be important modes of infection, especially in pigs. Aborted bovine fetuses may contain live virus.9,10
Insects, many of which have been shown to contain the virus, are unlikely to act as vectors. Other species, including European breeds of pigs in particular, and sheep, goats, camels and wild ruminants may serve as a source of the virus for cattle. Although there may be rare exceptions,11 it is doubtful that recovered animals act as carriers for more than a few days. Because of the failure of the virus to persist outside the body, rinderpest can be controlled by interrupting its transmission.12
Cattle and buffalo of all ages are susceptible to rinderpest, unless they have been vaccinated or have recovered from a previous infection or, in the case of calves, they have received colostral antibodies. European breeds of cattle are believed to be more susceptible than zebu cattle, but zebu cattle without antibodies from previous exposure or vaccination are fully susceptible. For example, the interruption of routine rinderpest vaccination in Central and West Africa in the 1970s was believed to be a major factor in the epidemics that ravaged zebu cattle populations in that region a few years later.13 Rinderpest used to occur in explosive outbreaks when it was first introduced to a herd and it would spread easily to other in-contact herds. This was particularly common among nomadic herds that seasonally migrate over long distances in search of pasture and water. Any other legal or illegal movement of animals incubating the disease could be a mode of spread. Cattle raids and communal grazing can be risk factors. Other ruminants and pigs in contact with infected cattle or buffalo may develop the disease.
The virus is present in the blood, tissues, secretions and excretions of infected animals, reaching its peak of concentration at about the height of the temperature reaction and subsiding gradually to disappear about a week after the temperature returns to normal in those animals that recover. The risk of transmission is therefore greatest during the febrile stage. The virus does not persist outside the host for more than a few hours at normal temperatures. It is inactivated in cadavers within 24 h as a result of pH changes and putrefaction, and it is readily destroyed by heat, drying and most disinfectants. Even in untreated premises, it survives for only a few days. However, it is relatively resistant to cold and may survive for as long as 1 month in blood kept under refrigeration. The risk of transmission can therefore be greatly minimized by applying appropriate sanitary and other control measures.
Immunity after a natural infection or by vaccination is long and for all practical purposes, persists for life. The protection is associated with the induction of humoral antibodies, first IgM and later, IgG and IgA, which are detectable by enzyme immunoassay.14 The disease is also associated with immunosuppression because the virus causes extensive necrosis of lymphocytes throughout the body. Older live vaccines can also cause immunosuppression. However, the newer tissue culture vaccine does not and can be simultaneously administered with other vaccines, for example, FMD and contagious bovine pleuropneumonia vaccines, without any diminished responses to any of the immunogens used.
Rinderpest can be experimentally reproduced by bringing susceptible animals in close contact with an infected one or by directly inoculating with blood or tissues from an infected animal or tissue culture. Rabbits can be artificially infected and this was made use of in the production of a lapinized virus vaccine.
Rinderpest has been one of the major diseases of cattle that occur in the form of epidemics. It is a List A diseases by OIE classification. Under extensive systems of management as practised in many African and Asian countries, the disease easily spreads across national boundaries and can involve most of the national herds of cattle and buffalo. Losses can be colossal and are due to deaths, loss of productivity and cost of effective prevention and control. During the outbreaks that occurred in Africa in the 1980s, millions of cattle were affected in the central and western regions. Reports from Nigeria indicated a death toll of 0.4 million infected cattle in 1983 and that the toll was higher in poorer countries that could not procure adequate doses of the vaccine. Fortunately, the situation has improved considerably due to the vaccination and surveillance programs of the Global Rinderpest Eradication Program (GREP) and the Pan African Rinderpest Campaign (PARC).
The virus is inhaled in infected droplets; it penetrates through the epithelium of the upper respiratory track and multiplies in tonsils and regional lymph nodes. From these sites, the virus enters the blood in mononuclear cells and is disseminated throughout the body, intimately associated with leukocytes and only a small proportion free in plasma. The virus has a high degree of affinity for lymphoid tissues and alimentary mucosa and replicates in monocytes, lymphocytes and epithelial cells.11,15 There is a striking destruction of lymphocytes in tissues resulting in marked leukopenia. Lymphocytes are destroyed by apoptosis as well as necrosis. The focal, necrotic stomatitis and enteritis which are characteristic of the disease are the direct result of viral infection and replication in epithelial cells in the alimentary tract. However, because the virus induces a strong antibody response shortly after infection, there is a rapid decline and elimination of virus from the body as clinical signs and lesions become manifest. Death is usually from severe dehydration, but in less acute cases, death may be from activated latent parasitic or bacterial infections which are exacerbated because the animal is immunosuppressed as a result of the destruction of lymphoid organs by the virus.
The following descriptions present the principal clinical signs of classical rinderpest but it must be remembered that an almost unlimited series of variations in syndromes may be encountered depending on the virulence of the strain of virus, the susceptibility of the host, and the presence or absence of concurrent diseases. Most outbreaks reported recently have been usually mild in cattle. In general, clinical signs may be peracute, acute, subacute or inapparent (in species other than cattle and buffalo).
The peracute form is not common except after experimental administration of the virus. It is characterized by high fever, congested mucous membranes, respiratory distress and death 1–3 d later.
Acute cases may be seen in naive cattle in areas or countries that were previously free of the disease. An incubation period of 6–9 d is usual. The first stage of the disease is several days of high fever (40.5–41.5°C; 105–107°F), without mucosal lesions (phase of prodromal fever). Anorexia, a fall in milk yield, lacrimation and a harsh, staring coat accompany the fever and this corresponds to the period of peak virus production in tissues. This is followed by the mucosal phase characterized by inflammation of buccal, nasal and conjunctival mucosae and, in some cases, hyperemia of vaginal mucosa and swelling of vulva. The lacrimation becomes more profuse and then purulent and is accompanied by blepharospasm. Bubbly salivation of clear blood-stained saliva is followed by purulent saliva and halitosis. A serous nasal discharge similarly becomes purulent. Discrete, grayish, raised necrotic lesions (1–5 mm in diameter) develop, appearing first on the inside of the lower lip and adjacent gum, on the cheek mucosa at the commissures, and on the lower surface of the tongue. Later they become general in the mouth, including the dorsum of the tongue, and may become so extensive that they coalesce. Similar lesions are common on nasal, vulval and vaginal mucosae. The necrotic material sloughs, leaving raw, red areas with sharp edges and these may coalesce to form shallow ulcers. Vesicles are not present.
Severe diarrhea, and sometimes dysentery with tenesmus, appear as lesions develop in abomasum and intestines. Skin lesions affecting the perineum, scrotum, flanks, inner aspects of thighs and the neck are less common. The skin becomes moist and reddened and later covered with scabs.
After a period of illness lasting from 3–5 d, there is a sudden fall in temperature, accompanied by exacerbation of the mucosal lesions. Other signs include dyspnea, cough, diarrhea, severe dehydration and sometimes abdominal pain. Prostration and a further fall in body temperature to subnormal levels occur on days 6–12, after which death usually occurs within 24 h. A few animals may survive and go into a convalescent phase during which the mucosal lesions heal rapidly, the diarrhea eventually stops and recovery of body condition takes several weeks. Pregnant cattle may abort at this stage, discharging infective virus in the fetus and vaginal secretions for up to 24 h.10
In enzootic areas, both a subacute form and a skin form occur with lower morbidity and mortality. In the subacute form, the temperature reaction is mild and the accompanying anorexia and malaise are not marked. The inflammation of the mucosae is catarrhal only and there is no dysentery. In the skin form, the systemic reaction is absent and small pustules develop on the neck, over the withers, inside the thighs and on the scrotum. Most affected animals recover and convalescence is short. However, because of the severe lymphocytolysis, latent pathogens, particularly Anaplasma marginale, are often activated and the resulting disease may overshadow the primary rinderpest.
Signs and lesions similar to those which occur in cattle develop in sheep and goats and in Asian pigs. The disease in European pigs is clinically inapparent and wild ungulates exhibit a wide range of clinical signs, from severe to mild. Keratoconjunctivitis has been described in buffaloes and kudus affected with lineage 2 virus.4
A marked leucopenia occurs at the height of the infection and after vaccination in cattle and in experimentally infected sheep and pigs. The total count usually falls to below 4000 μL and is due to a precipitous drop in lymphocytes. With diarrhea, animals also become severely dehydrated. Later, they may show neutrophilia.
Various methods for diagnosing rinderpest have been described and basically involve identification of the agent and serological tests.1 A rapid chromatographic strip test (Penside test) that can detect rinderpest antigen in lachrymal fluid16 is a useful tool for field personnel. In areas where there had been recent outbreaks, a presumptive diagnosis also can be made on the basis of the history, clinical signs and postmortem findings. Since the prevalence of the disease is decreasing, it is recommended that for each outbreak, the virus should be isolated, its lineage identified and its virulence in cattle assessed.1 Antibody detection in paired serum samples is not recommended during an outbreak because of the length of time required to confirm a diagnosis but it is used for disease surveillance and vaccine evaluation. For antigen detection and virus isolation, the key to diagnostic success is the collection of suitable samples at the optimum time (3–5 d after fever commences) from many animals rather than many samples from one sick or dead animal. The proportion of positive reactors falls sharply after diarrhea commences and in moribund or dead animals.
A technique suitable for laboratory and field use is the agar gel diffusion (AGID) technique in which needle biopsy samples of lymph node are used as antigen. Other satisfactory methods of detecting rinderpest antigen in feces, buccal scrapings, and ocular and nasal discharges in the early stages of the disease are the complement fixation, counterimmunoelectrophoresis (CIEP),17 immunofluorescence, immunohistology and passive hemagglutination tests. The virus can be detected immunohistochemically in the tonsil despite marked autolytic changes.18 Using specific cDNA probes, isolates of rinderpest and PPR viruses can now be differentiated19 and a test employing the polymerase chain reaction has been developed that can detect viral RNA in tissues otherwise unsuitable for standard techniques.
The isolation of the virus in tissue culture and its identification is best done with washed leukocytes harvested from blood buffy coat or from fresh lymph node. Rapid virus isolation is possible using continuous growing lines of bovine T-lymphocytes.9
For antibody detection, a CFT is of limited value on a herd basis. Antibodies in serum reach peak levels about 14 d after the development of clinical disease. In animals which have recovered for longer periods, the antibody level may be so low that the test is unsatisfactory. For this reason, the serum neutralization test is used more widely, even though it is time consuming and involves the use of tissue culture facilities. Neutralizing antibodies remain detectable for years and they correlate very closely with clinical and virological immunity. This test is at present the most suitable assay for surveillance for virus circulating in the field and for monitoring the efficiency of a recent vaccination campaign. Other available serological tests include those based on the detection of fluorescent antibody and immunoperoxidase,11 an ELISA which is accurate and easy to perform20 and can differentiate between rinderpest and PPR,21 and a rapid dot-enzyme immunoassay test suitable for field use.22
Confirmation by the experimental transmission of the disease is expensive and dangerous unless isolation facilities with maximum security are available. The recipient group should include one or more animals known to be immune to rinderpest. The intravenous inoculation of 5 mL of blood from an affected animal at the height of the disease into susceptible cattle is followed by the development of signs in 3–10 d. Sheep as recipient animals may only show mild febrile reaction and mucosal erosions.
The important necropsy findings are in the alimentary and upper respiratory tracts and in the external genitalia in females. The carcass is dehydrated, emaciated and soiled with fetid feces. Small, discrete, necrotic areas develop on the oral mucosa and separation of the necrotic material leaves sharply walled, deep erosions with a red floor which may coalesce to form large erosions or ulcers. These lesions extend to the pharynx, upper esophagus and abomasum, particularly the pyloric region. The forestomachs are spared and lesions are mild in the small intestine except at the Peyer’s patches which are swollen, hemorrhagic and necrotic. Severe changes occur in the mucosa and lymphoid nodules in the large intestine, particularly at the cecocolic junction. Zones of hemorrhage and erythema running transversely across the colonic mucosa produce a characteristic striped appearance, the so-called ‘zebra stripes’. The nasal turbinates and septa are coated with a tenacious mucopurulent exudate beneath which is an eroded and ulcerated surface. Lesions may extend to the upper trachea but not beyond and the lungs are usually not affected. Congestion, swelling and erosion of the vulval and vaginal mucosae may occur.
Histologically, the mucosal changes are characterized by necrosis of stratified squamous epithelium of the upper alimentary tract and necrosis of crypts in the intestine, with resulting erosions and superficial ulcers. Inflammatory cells are minimal but multinucleated syncytia are characteristic. Intranuclear and intracytoplasmic viral inclusion bodies may be present, especially in the tonsils. Lymph nodes and spleen may appear normal grossly but microscopically, they show characteristic massive necrosis of lymphocytes.
Materials sent for laboratory examination should include fixed sections of lymph node, tonsil and alimentary tract lesions, as well as fresh spleen, blood and alimentary tract for antigen detection or virus isolation.
Rinderpest should be suspected when a number of cattle or buffalo are affected by a febrile, fatal, highly infectious disease with characteristic signs. FMD and hemorrhagic septicemia are other diseases which occur in epidemics but are sufficiently dissimilar to present no difficulty in differentiation. Malignant catarrhal fever (MCF) and bovine virus diarrhea/mucosal disease (BVD/MD) present the major difficulty in diagnosis. MCF rarely affects many animals in one herd and is characterized by specific eye lesions and nervous signs. BVD/MD occurs either in explosive outbreaks like rinderpest but the mortality rate is low, or it occurs sporadically, but is uniformly fatal. The postmortem lesions of rinderpest and BVD/MD are virtually identical. Jembrana disease in Indonesia is another highly fatal disease of cattle and buffalo but anemia will be a feature and the microscopic lesions are different from those of rinderpest. Infectious bovine rhinotracheitis may produce similar mucosal lesions. In sheep and goats, PPR presents the greatest problem in differentiation but pneumonia is usually a feature of PPR but not rinderpest. If only sheep and goats are affected in an outbreak, it is most likely PPR. Other diseases to be considered are bluetongue, sheep, and goatpox and Nairobi sheep disease.
Treatment is ineffective and should not be undertaken because of the danger of disseminating the disease. Vaccines are of no value in treating already infected animals or those infected up to 48 hours after vaccination.
Rinderpest is a simple disease and outbreaks can be effectively controlled by slaughter and rigid quarantine measures. In endemic areas, control used to be by annual vaccination and surveillance. Preparation of the vaccines is simplified by the common antigenicity of all known strains of the rinderpest virus, thus a vaccine prepared from one strain will protect against all other strains. Rinderpest vaccine protects goats against infection with the virus of PPR, probably for life despite antigenic differences between the two viruses. Although rinderpest virus has no serological similarity to BVD virus, immunity to the latter is believed to provide some protection against infection with the former.
The introduction of rinderpest to a previously uninfected country is most likely to occur through importation of infected animals, particularly to zoological gardens, but the possibility does exist that carcass meat infected with the virus could be a portal of entry. Uncooked, infected garbage has been shown to be capable of infecting pigs which subsequently spread the infection to other pigs and to cattle. Prevention of the introduction of ruminants and pigs from known infected areas is routinely practiced in countries which do not have the disease. Countries with land borders to enzootic areas can usually be adequately protected by satisfactory quarantine at the border and the erection of immune barrier zones.
When epidemic occurs in normally free areas, it is necessary to prevent movement of both living animals and fresh animal products. All susceptible animals in infected and in-contact groups must be slaughtered and disposed of on the respective farms. All ruminants and pigs must be considered susceptible and special attention should be given to native fauna. Infected premises should be cleaned and disinfected. Solutions of caustic soda and lysol are ideal and the premises can be restocked after 1 week. When outbreaks are threatened or when an outbreak is extensive and likely to get out of control, all ruminants and pigs in the danger area should be vaccinated with an attenuated virus vaccine.
In endemic areas, control depends upon the use of an efficient vaccination procedure and disease surveillance at national, regional or continental level as is being done under the auspices of GREP. For example, African countries successfully initiated the Joint Project 15 in 1962–1976 followed later with a Pan-African Rinderpest Campaign (PARC) to rid the whole continent of the disease. The initial step was to vaccinate all animals in each national herd annually until the immune status exceeded 90%. Thereafter, calves were vaccinated annually and revaccinated the following year until there were no more outbreaks for at least 5 years. Currently, there is periodic surveillance to monitor the immune status of each national herd and to deal quickly with any new outbreaks by control of animal movement and ring vaccination of all surrounding herds. Suitable legal and administrative powers are necessary for the proper use of control by vaccination. The ideal vaccine is one which can be produced with varying degrees of attenuation suitable for safe and effective vaccination of cattle with different levels of susceptibility. It should also be highly thermostable, inexpensive and easy to administer under current systems of animal husbandry in Africa and Asia.
The second most important problem associated with rinderpest vaccination is the activation of existing latent infections in vaccinated animals. In general, the problem is greater after the use of less attenuated vaccines. Although protozoal infections present the greatest risk, bacterial and viral diseases may also be activated.23 Vaccination of cattle with ears heavily infested with the tick Rhipicephalus appendiculatus should be avoided.
Calves present a special problem. If they receive no antibodies in the colostrum, they can be successfully vaccinated at 1 d of age, but if they are from immune cows the vaccination will be ineffective if carried out while they still have high levels of maternally derived antibodies. Colostrum-fed calves from immune cows are believed to be passively immune for periods of 4–8 months, the duration depending upon the immune status of the dam. A recent study recommended vaccinating calves after 3–3.5 months of age when maternal antibodies would have waned.24 The possibility that vaccinated animals can be infected and become active carriers of the virus is unresolved, but this is unlikely to occur with tissue culture vaccines. With the older vaccines, vaccinated calves or calves with colostral antibody were susceptible to experimental intranasal infection with the rinderpest virus, which was subsequently excreted to susceptible in-contact animals.25
In areas where PPR is endemic, antibodies to PPR in cattle, sheep and goats could prevent an immune response to rinderpest vaccine. Since PPR antibodies are both cross-neutralizing and cross-protective against rinderpest virus, further vaccination in the presence of these antibodies would be wasteful.26
A dual vaccine against rinderpest and contagious bovine pleuropneumonia has been in use in Africa but its efficiency against contagious bovine pleuropneumonia (CBPP) is less than maximal and it is not generally recommended.27
The principal vaccine used to control rinderpest throughout the world is the tissue culture rinderpest vaccine (TCRV) produced in calf kidney cells14,28 for cattle. Before its development, attenuated vaccines were prepared by passage of the virus in goats, rabbits and chicken eggs to produce caprinized, laprinized and avianized vaccines, respectively. TCRV is easy and cheap to produce and can be freeze dried or lyophilized29 and therefore has a long shelf-life before it is reconstituted. Furthermore, it is capable of varying degrees of attenuation and is thus safer in all situations. Finally, it produces a life-long immunity and does not spread from vaccinated to in-contact cattle. Its main drawback is that after reconstitution, the vaccine must be used within a few hours unless refrigerated. The establishment of cold chains in the tropics thus adds to the cost of the vaccination program. Another drawback is the difficulty in distinguishing between antibodies due to infection and those due to vaccination since both lead to life-long immunity. Cultures should also be free of infection with BVD virus.23 The use of Vero cell line obviates this risk and a lyophilized vaccine that can be kept without refrigeration at high ambient temperatures for up to 2 months has been developed from this cell line.9 TCRV used for cattle is suitable for use in buffaloes and also in sheep and goats which can also be protected against rinderpest by vaccination with attenuated PPR virus.30
The measles vaccine protects calves against rinderpest at an age when ordinary rinderpest vaccines are ineffective due to interference from colostral antibody. It is also an efficient vaccine for use in adult cattle.31 Recombinant vaccines against rinderpest are being developed and tested to assess the duration of immunity conferred. A highly attenuated vaccinia virus double recombinant that expressed both the F and H genes of rinderpest virus was found to protect cattle against experimental rinderpest and did not cause pox lesions.32 The vaccine is heat-stable and calves can be vaccinated at any age, even in the presence of colostral antibodies.33 A variant of this vaccine which expressed only the H protein protected experimental cattle for up to 3 years.34 Cattle can also be protected against rinderpest and lumpy skin disease (LSD) with a recombinant capripoxvirus vaccine expressing the fusion gene of rinderpest virus.35 In another study, two of four vaccinated animals were solidly protected from virulent rinderpest challenge after 2 years, and all four from challenge with virulent LSD virus.35 The recombinant vaccine showed no loss of potency when stored lyophilized at 4°C for up to 1 year. Nevertheless, there is still the need to improve the cold chain for many veterinary products and samples in parts of Africa and Asia.
Plowright W. Rinderpest virus virology monographs. Vienna and New York: Springer Verlag, 1986.
Rossiter PB, Wamwayi HM. Surveillance and monitoring programmes in the control of rinderpest: a review. Trop Anim Health Prod. 1989;21:89-99.
Scott GR. Cattle plague. In: Sewell MMH, Brocklesby DW, editors. Handbook on animal diseases in the tropics. 4th edn. London: Baillère Tindall; 1990:287-292.
OIE. Manual of diagnostic tests and vaccines for terrestrial animals. http://www.oie.int/eng/normes/mmanual/A_00027.htm, 2004. Chapter 2.1.4. 5th edn.
Rossiter PB. Rinderpest. Coetzer JAW, Tustin RC, editors. Infectious diseases of livestock, 2nd edn., Vol 2. Cape Town: Oxford University Press, 2004;629-659.
1 OIE. Manual of diagnostic tests and vaccines for terrestrial animals. http://www.oie.int/eng/normes/mmanual/A_00027.htm, 2004. Chapter 2.1.4. 5th edn.
2 Rossiter PB. Rinderpest. Coetzer JAW, Tustin RC, editors. Infectious diseases of livestock, 2nd edn., Vol 2. Cape Town: Oxford University Press, 2004;629-659.
3 Barret T, et al. Rev Sci Tech. 1993;12:865.
4 Kock RA, et al. Vet Rec. 1999;145:275.
5 Scott GR, Ramachandran S. Trans R Soc Trop Med Hyg. 1974;68:276.
6 Dutta J, et al. Indian Vet J. 1991;68:99.
7 Abraham A, et al. Refuah Vet. 1984;41:112.
8 Mariner JC, Roeder PL. Vet Rec. 2003;152:641.
9 Groocock CM. Foreign Anim Dis Rep. 1992;20:14.
10 Wafula JS, et al. Vet Rec. 1989;124:485.
11 Joshi RC, et al. Trop Anim Health Prod. 1984;16:67.
12 Taylor WP, et al. Vet Microbiol. 1995;44:359.
13 Ikede BO. Trop Vet. 1984;2:1.
14 Anderson J, et al. Res Vet Sci. 1982;32:242.
15 Re-Nores JE, McCullough KC. J Virol. 1996;70(44):19.
16 Bruning A, et al. J Virol Methods. 1999;81:143.
17 Obi TU, Patrick D. J Hyg Camb. 1984;93:579.
18 Brown CC, et al. Res Vet Sci. 1996;60:182.
19 Diallo A, et al. J Virol Methods. 1989;23:127.
20 Sharma B, et al. Ind J Anim Sci. 1983;53:292.
21 Diallo A, et al. Vet Microbiol. 1995;44:307.
22 Afshar A, Myers DJ. Trop Anim Health Prod. 1986;18:209.
23 Scott GR. Prog Vet Microbiol Immunol. 1985;1:145-174.
24 Ertuk A, Burgu I. Etlik-Veteriner-Mikrobiyoloji-Dergisi. 2002;13:1.
25 Provost A. Rev Elev Med Vet Pays Trop. 1972;25:155.
26 Anderson J, McKay JA. Epidemiol Infect. 1994;112:225.
27 Jeggo MH, et al. Vet Rec. 1987;120:131.
28 Plowright W. J Hyg Camb. 1984;92:285.
29 Mariner JC. Vet Microbiol. 1990;22:119.
30 Couacy-Hymann E, et al. Res Vet Sci. 1995;59:106.
31 Provost A, et al. Rev Elev Med Vet Pays Trop. 1986;21:145.
32 Giavedoni L, et al. Proc Natl Acad Sci USA. 1991;88:8011.
33 Yilma TD. Vaccine. 1989;7:484.
Contagious disease of goats and sheep; endemic in west and central Africa, outbreaks in northeastern Africa, Middle East and Asia, high mortality in goats
Peste des petits ruminants (PPR) is associated with PPRV, a morbillivirus (family Paramyxoviridae) closely related to the rinderpest virus as well as the viruses of canine distemper in dogs, phocine distemper in seals, and measles in humans.1 Four lineages of PPRV have been identified; lineage 1 and 2 viruses in west Africa, lineage 3 in east Africa, Arabia and southern India, and lineage 4 in the Middle East and Asia subcontinent, reaching east as far as Nepal and Bangladesh.2 The African and Asian lineages (strains) of the virus have some biochemical and genetic differences, implying that both strains may have evolved separately.3 All four lineages have been shown to be genetically distinct from the rinderpest virus, thereby raising some doubt to the notion that PPRV might have evolved in the first half of the 20th century from goat-adapted rinderpest vaccines.
The disease occurs mostly in goats and sheep. Outbreaks were first described in West Africa in 1942 and the disease is now endemic in the region. In addition, outbreaks have been reported from much of sub-Saharan Africa north of the equator. Since the 1990s, outbreaks have been reported from the Arabian Peninsula as far north as Turkey and extending through Pakistan and India to Nepal and Bangladesh. It is possible that some of the earlier reports of rinderpest in sheep and goats in Asia might have been PPR outbreaks since the two diseases in these species are not easily distinguishable on clinical examination only. Cattle and pigs develop serum-neutralizing antibodies but no disease following experimental infection. Natural disease may occur in the wild sheep, gazelle and the deer but there are no known reservoirs in domestic animals and wildlife. Based on clinical signs and detection of antibodies, PPR and rinderpest viruses were suspected to be involved in a highly contagious disease of Ethiopian camels in 1995,4 but the role of the two viruses in camels requires further studies. PPR is not transmissible to humans.
Outbreaks invariably occur when new stock is introduced into a farm. In West Africa, this usually takes place when Sahelian goats and sheep believed to have high innate resistance to the virus are moved southwards and commingle with the dwarf breeds in the humid and sub-humid tropics. Such mingling occurs during seasonal migrations and religious festivals. Market goats do harbor and can transmit the virus. The first outbreaks in Saudi Arabia were associated with the importation of sheep from Africa or the return of unsold lambs from livestock markets.
Infection rates in enzootic areas are generally high (above 50%) and can be up to 90% of the flock during outbreaks. The percentage of sheep and goats with antibodies rises with age. The disease, however, is more severe in goats than in sheep and is rapidly fatal in young animals. Case–fatality rates are also much higher in goats (55–85%) than in sheep (less than 10%). Goats have also been more severely affected in the more recent outbreaks involving the virus of Asian lineage.5 There is no significant seasonal variation in the prevalence of the disease but since maternal antibodies are lost at about 4 months of age, the number of susceptible animals is likely to increase 3–4 months after peak kidding and lambing seasons.
As in rinderpest, close contact with an infected animal or contaminated fomites is required for the disease to spread. Large amounts of the virus are present in all body excretions and secretions, especially in diarrheic feces. Infection is mainly by inhalation but could also occur through the conjunctiva and oral mucosa.
Kids over 4 months and under 1 year of age are most susceptible to the disease. Sahelian breeds of sheep and goats are believed to be more resistant than the dwarf breeds in the humid and sub-humid zones of West Africa. In a particular flock, the risk of an out-break is greatly increased when a new stock is introduced or when animals are returned unsold from livestock markets. Recovered animals have lifetime immunity.
The disease can be experimentally transmitted through close contact with an infected animal or through inoculation of infected tissues or blood.
PPR is regarded as the most important disease of goats and sheep in West Africa and possibly in all countries where the disease occurs. In many of those countries, these animals are a major source of animal protein.
Like rinderpest, PPR requires close contact with an infected animal for transmission to occur. Nevertheless, since live goats and sheep are traded and may be carried over long distances, the disease can be easily introduced to a new herd or even a new country unknowingly from animals incubating PPR or showing only mild lesions.
PPR virus penetrates the retropharyngeal mucosa, sets up a viremia and specifically damages the alimentary, respiratory and lymphoid systems. Infected cells undergo necrosis, and in the respiratory system, also proliferation. Death may occur from severe diarrhea and dehydration, before respiratory lesions become severe, or is hastened by concurrent diseases such as pneumonic pasteurellosis, coccidiosis or coliform enteritis. Lymphoid necrosis is not as marked as in rinderpest and the possibility of immunosuppression has not been investigated. Most sheep and some adult goats recover.
The disease can be acute or subacute. The acute form is seen mainly in goats and is similar to rinderpest in cattle except that severe respiratory distress is a common feature of PPR. Signs generally appear 3–6 d after being in contact with an infected animal. A high fever (above 40°C) is accompanied by dullness, sneezing and serous discharge from the eyes and nostrils. A day or two later, discrete necrotic lesions develop in the mouth and extend over the entire oral mucosa, forming diphtheric plaques. There is profound halitosis and the animal is unable to eat because of a sore mouth and swollen lips. Nasal and ocular discharges become mucopurulent and the exudate dries up, matting the eyelids and partially occluding the external nares. Diarrhea develops 3–4 d after the onset of fever. It is profuse and feces may be mucoid and blood tinged. Dyspnea and coughing occur later and the respiratory signs are aggravated when there is secondary bacterial pneumonia. Erosions have been described in the vulva and prepuce. Abortions have been reported during outbreaks in India.5 Death usually occurs within 1 week of the onset of illness.
Subacute forms are more common in sheep but they also occur in goats. The signs and lesions are less marked and a few animals may die within 2 weeks, but most recover. Contagious ecthyma (orf) may complicate the labial lesions or develop in surviving animals.
A leukopenia occurs but is not as marked as in rinderpest. As diarrhea develops, there is a progressive hemoconcentration and low serum sodium and potassium.6
Diagnostic techniques used in the past were virus neutralization test (VNT), agar gel immunodiffusion (AGID), complement fixation, counter immunoelectrophoresis (CIEP), virus isolation in cell cultures, and animal inoculation. Some are still used on a herd basis and VNT is the prescribed test for international trade.7 More recently, competitive or blocking enzyme-linked immunosorbent assays (c-ELISAs) have been developed based on monoclonal antibodies specific for the nucleocapsid (N) or hemagglutinin (H) proteins of PPR and rinderpest viruses, and which enable differential diagnosis of the two viruses.6 The efficacy of c-ELISA compares very well with virus neutralization test for detection and titration of antibodies to PPRV in goats and sheep.8 Viral antigen can also be detected in buffy coat, body secretions, feces, lymph node and tonsils by immunohistochemical9-11 and dot-ELISA12 methods as well as by AGID and CIEP. Furthermore, the reverse transcription-polymerase chain reaction (RT-PCR) has been reported to be more rapid and far more sensitive than conventional titration technique on Vero cells.13 Unlike rinderpest, PPR viral antigen is still high in tissues of animals dying from the disease.
The carcass is severely dehydrated, the hindquarters are soiled with fluid feces, and crusts of exudate are present around eyes, nose and lips. Discrete or extensive areas of erosion, necrosis, and ulceration are present in the oral mucosa, pharynx, and upper esophagus and may extend to the abomasum and distal small intestine. Hemorrhagic ulceration is marked in the ileocecal region, colon and rectum where they produce typical ‘zebra stripes’. Regional lymph nodes are enlarged and wet and the spleen may be enlarged. Severe lesions are often present throughout the respiratory tract. A mucopurulent exudate extends from the nasal opening to the larynx whereas the trachea and bronchi may be hyperemic and contain froth due to pulmonary congestion and edema. An interstitial pneumonia is usually present.9,10 Grossly, the pneumonia is diffuse or more commonly, antero-ventral or apical. With bacterial complications, there will be purulent or fibrinous bronchopneumonia and pleuritis.
Microscopic lesions in the alimentary tract are similar to those in rinderpest but are often more severe. In the early stages, syncytial cells are present in the oral mucosa and intracytoplasmic eosinophilic inclusion bodies in intestinal crypt epithelium. The respiratory tract shows proliferative rhinotracheitis, bronchitis, bronchiolitis, proliferation of type II pneumocytes, and formation of huge syncytial giant cells. Intracytoplasmic and intranuclear inclusion bodies are common in these cells. In a recent immunohistochemical study of natural PPR pneumonias in goats, viral antigens were found most frequently in the cytoplasm and rarely in the nucleus of lower respiratory epithelial cells, type 11 pneumocytes, syncytial cells and alveolar macrophages.14 Lymphoid organs are depleted of lymphocytes but not usually as marked as in rinderpest.
For diagnostic purpose, specimens should be collected from several live animals and should include swabs of conjunctival, nasal and buccal mucosae, as well as whole blood in anticoagulant for virus isolation and other tests. At necropsy, the following specimens should be collected for virology and histopathology:
Other diseases that cause diarrhea or pneumonia in sheep and goats may pose a diagnostic challenge but a history of recent introduction of new stock and the clinical and postmortem findings of stomatitis, enteritis and syncytial giant cell pneumonia are typical for PPR. Laboratory tests are required to rule out rinderpest. Other diseases to be considered are:
Valuable sick animals in the early stages of the disease should be isolated and given hyperimmune serum, which may be obtained from cattle hyperimmunized against rinderpest. Supportive treatment includes fluid therapy for dehydration and antibiotics to prevent secondary bacterial infections. Lesions around the eyes, nostrils and mouth should be cleaned, and good nursing provided.
The disease can be prevented by not introducing new stock from unknown sources, especially animals bought at livestock markets. In addition, animals returned unsold from markets should be segregated unless the entire herd or flock has been vaccinated. The tissue culture rinderpest vaccine is effective but its use in enzootic areas is not as organized as it is for rinderpest. Kids and lambs should be vaccinated at 3–4 months of age by which time maternal antibodies would have waned. Newly developed recombinant vaccinia15 or capripox16 viruses expressing the fusion (F) and hemagglutinin (H) protein genes of the rinderpest virus are also effective against PPR. More recently, a homologous PPRV tissue culture vaccine was produced by serial passages in Vero cells. This vaccine is now widely used in the control of PPR.17 The homologous vaccine has the advantage that it avoids confusion with rinderpest vaccine when serological surveys are performed.7
Scott GR. Goat plague. In: Sewell MMH, Brocklesby DW, editors. Handbook on animal diseases in the tropics. 4th edn. London: Baillière Tindall; 1990:312-315.
OIE. Manual of diagnostic tests and vaccines for terrestrial animals. http://www.oie.int/eng/normes/mmanual/A_00028.htm, 2004. Chapter 2.1.5. 5th edn.
Rossiter PB. Peste des petits ruminants. Coetzer JAW, Tustin RC, editors. Infectious diseases of livestock, 2nd edn., vol 2. Cape Town: Oxford University Press, 2004;660-672.
1 Murphy FA, et al. Virus taxonomy Arch Virol Suppl. 1995;10:271.
2 Pronab D, et al. Vet Microbiol. 2002;88:153.
3 Abu Elzein EME, et al. Vet Rec. 1990;127:309.
4 Roger F, et al. Rev Med Vet. 2001;152:265.
5 Pankaj K, et al. Indian J Vet Pathol. 2002;26:15.
6 Diallo A, et al. Vet Microbiol. 1995;44:307.
7 OIE. Manual of diagnostic tests and vaccines for terrestrial animals. http://www.oie.int/eng/normes/mmanual/A_00028.htm, 2004. Chapter 2.1.5. 5th edn.
8 Singh RP, et al. Vet Microbiol. 2004;98:3.
9 Bundza A, et al. Can J Vet Res. 1988;52:46.
10 Brown CC, et al. Vet Pathol. 1991;28:166.
11 Diallo A, et al. J Virol Methods. 1989;23:127.
12 Obi TU, Ojeh CK. J Clin Microbiol. 1990;27:2096.
13 Couacy HE, et al. J Virol Methods. 2002;100:17.
14 Yener Z, et al. Small Ruminant Res. 2004;51:273.
15 Jones L, et al. Vaccine. 1993;11:961.
16 Romero CH, et al. Vaccine. 1995;13:36.
17 Diallo A, et al. Vaccines for OIE list A and emerging diseases. Basel Switzerland: S Karger AG, 2003;113-119. Proceedings of a symposium, Ames, Iowa, USA, 16–18 September 2002
Jembrana disease is the name of a highly fatal, infectious, disease that occurs in Bali cattle (Bos javanicus) and buffaloes (Bubalus bubalis) on the island of Bali in Indonesia. The disease is endemic in areas of Indonesia, but the severe disease of the initial outbreak has modified with time.
The disease is caused by a lentivirus, genetically related but distinct from bovine immunodeficiency virus.1 Both viruses are present in Bali cattle but the bovine immunodeficiency virus has been identified in cattle on islands where Jembrana disease has not occurred.2 Jembrana disease virus has not been propagated in vitro and there is difficulty in differentiating infection with the two viruses by serological methods.3,4
The disease originally occurred in Jembrana district on the Island of Bali, Indonesia in 1964 and rapidly spread to the rest of the island resulting in the deaths of approximately 17% of Bali cattle.5 Since 1964 the disease has been endemic on Bali island but with lower morbidity and mortality rates. It has subsequently spread to the Indoensian islands of Sumatra, Java and Kalimantan, producing initial epidemic diease with high mortality followed by endemic disease with lower morbidity and mortality.5
Transmission probably occurs by direct contact with infective secretions in the acute phase of the disease and by mechanical transmission by hematophagous insects or mechanically by needles during mass vaccination of animals for the control of diseases, such as hemorrhagic septicemia.6
The disease can be experimentally transmitted by IV or intraperitoneal inoculation of blood or spleen into B. javanicus. The virus is present in high titer in the blood during the febrile phase and in the saliva and milk.6,7 In B. javanicus an incubation period of 4–12 days is followed by fever lasting from 5 to 12 days and clinical signs typical of the enzootic form of the disease. Persistent infection occurs for periods of at least 2 years following recovery.
Experimental challenge of B. indicus, B. taurus and crossbred (B. javanicus and B. indicus) cattle results in only a transient febrile response, mild clinical disease and a viremia that persist for 3 months, although antibody persists for at least 4 years following infection.8 Infection, as determined by antibody response, but not clinical disease can be transmitted experimentally to pigs, sheep, goats and buffaloes.5
Jembrana disease is not typical of other lentivirus infections, which are characterized by chronic progressive disease with long incubation periods. There is a high viremia during the febrile stage. Initial virus proliferaton in the spleen is followed by widespread dissemination during a second proliferative phase and infection in lymph nodes, lungs, bone marrow, liver and kidney. The specific cell types infected by Jembrana virus have not yet been identified but appear to be of lymphocyte origin or of the monocyte/macrophage lineage.9
Natural clinical disease is reported only in B. javanicus, other cattle types and buffalo are subclinically infected in natural outbreaks. Clinical signs include fever (40–42°C; 104–107°F), which lasts up to 12 days, anorexia, generalized lymphadenopathy, nasal discharge, increased salivation and anemia. In severely affected cattle there is diarrhea followed by dysentery. Mucosal erosions can occur but are rare. Hemorrhages are present in the vagina, mouth and occasionally the anterior chamber of the eye in the severe disease.
Where the disease is enzootic and less severe in presentation clinical signs include inappetence, fever, lethargy, reluctance to move, enlargement of the superficial lymph nodes, mild erisons of the oral mucosa and diarrhea.
During the febrile period there is a moderate normocytic normochromic anemia and a leukopenia with lymphopenia, eosinopenia and thrombocytopenia.7 Bone marrow shows no changes historically. Elevated blood urea concentrations and diminished total plasma protein are seen in B. javanicus but not B. taurus.6 An ELISA test and an agar gel immunodiffusion test can be used for serological surveys. Both are specific but the ELISA test has greater sensitivity but limited sensitivity.4,10
Necropsy lesions in B. javanicus include generalized lymphadenopathy, with enlargements up to 20-fold, and generalized hemorrhages. The spleen is enlarged to three to four times its normal size. Histologically, there its vasculitis and perivasculitis and follicular atrophy in the spleen and lymph nodes, and parafollicular proliferation of mononuclear cells in intestinal lymphoid tissue.5,9
Treatment is supportive. There is currently no specific control. Vaccination has been attempted using virus-containing plasma and spleen tissue from acutely affected cattle with the virus inactivated with triton X-100 and the vaccine adjuvanted with either mineral oil or Freund’s incomplete adjuvant.11 Protection is only partial and not of real value in control.
1 Chadwick BJ, et al. J Gen. Virol. 1995;76:1637.
2 Barboni P, et al. Vet Microbiol. 2001;80:313.
3 Desport M, et al. J Virol Methods. 2005;124:135.
4 Stewart M, et al. J Clin Microbiol. 2005;43:5574.
5 Wilcox GE. Aust Vet J. 1997;75:492.
6 Soeharsono S, et al. Epidemiol Infect. 1995;115:367.
7 Soeranto M, et al. J Comp Pathol. 1990;103:61.
8 Soeharsono S, et al. J Comp Pathol. 1995;112:391.
9 Chadwick BJ, et al. J Gen Virol. 1998;79:101.
10 Hartaningsih N, et al. Vet Microbiol. 1994;39:15.
11 Hartaningsih N, et al. Vet Immunol Immunopathol. 2001;78:163.
This is a tick-transmitted disease of small ruminants, particularly sheep, associated with the Nairobi sheep disease virus (NSDV), a bunyavirus (genus Nairovirus) and characterized by fever, hemorrhagic gastroenteritis, abortion and high mortality.1,2 It is endemic in East and Central Africa (Kenya, Uganda, Tanzania, Ruanda, Somalia, and Ethiopia) and antibodies to the virus and other bunyaviruses have been detected in southern and northeastern Africa and Sri Lanka.3,4 Genetic and serologic data have shown that the Ganjam virus in Indian goats is an Asian variant of NSDV.5 Other antigenically related viruses are the Crimean-Congo hemorrhagic fever virus in humans and the Dugbe fever virus in west African cattle. NSD virus does not affect cattle but can cause a mild febrile disease in humans, hence a zoonosis. The most common vector is the brown ear tick Rhipicephalus appendiculatus, but other species may be involved, as well as the bont tick, Amblyomma variegatum. Transmission by R. appendicaltus is both trans-stadial and trans-ovarial. Animals in endemic areas are usually immune and the virus can persist in ticks for long periods, more than two years in unfed adults.
Clinical disease occurs when susceptible animals are moved into endemic areas (e.g. for marketing purposes) or when there is a breakdown in tick control measures. Outbreaks occur outside endemic areas when there has been unusual increase in tick population brought about by excessive or prolonged rains. There are differences in susceptibility among different breeds of sheep and goats, and unlike in most other diseases, some indigenous breeds are more susceptible than exotic breeds. A sudden onset of fever is followed by anorexia, nasal discharge, dyspnea and a severe diarrhea, sometimes with dysentery, abortion and death in 3–9 d. The case–mortality rate is 30–90% but is lower in goats. The necropsy picture is typical of a hemorrhagic diathesis and consists of hemorrhages on serous surfaces of visceral organs and on mucosal surfaces, particularly the abomasum, colon and female genital tract. Lymph nodes are enlarged. Later, a hemorrhagic gastroenteritis becomes more obvious and there may be zebra striping of the colon and rectum.1 The uterus and fetal skin are hemorrhagic. Ticks are likely to be found in the body, especially in the ears and head. Common histopathologic lesions outside the gastrointestinal tract include myocardial degeneration, nephritis and necrosis of the gall bladder.1
Differential diagnoses include peste des petits ruminants (PPR), rinderpest, Rift Valley fever, heartwater, parasitic gastroenteritis and salmonellosis, all to be confirmed by laboratory tests. Specimens for laboratory diagnosis should include uncoagulated blood, mesenteric lymph node and spleen collected safely to avoid aerosol infections. The virus is first isolated in tissue culture or in infant mice, and the disease can be reproduced in susceptible sheep. The recommended serological test is the indirect fluorescent antibody test, but others are the complement fixation test (CFT) and the indirect hemagglutination test.1 For viral identification, the recommended tests are immunofluorescence, agar gel immunodiffusion, CFT and ELISA. Apparently, there are no reports of involving the use of reverse transcription-polymerase chain reaction (RT-PCR) test in small ruminants but the test was found to be less sensitive in ticks.6 There is no treatment for NSD but the disease can be controlled by vaccination and vector control. Animals to be moved to endemic areas should receive a killed tissue culture vaccine or an attenuated live virus vaccine.
1 OIE. Manual of diagnostic tests and vaccines for terrestrial animals. http://www.oie.int/eng/normes/mmanual/A_00128.htm, 2004. Chapter 2.10.2. 5th edn.
2 Davies FG, Terpstra C. Coetzer JA, Tustin RC, editors. Infectious diseases of livestock, 2nd edn., vol 2. Cape Town: Oxford University Press, 2004;1071-1076.
3 Perera LP, et al. Ann Trop Med Parasitol. 1996:90-91.
4 Scott GR. Sewell MMH, Brocklesby DW, editors. Handbook on animal diseases in the tropics, 4th edn. London: Baillière Tindall. 1990:335-337.
Alcelaphine herpesvirus-1, the wildebeest-associated malignant catarrhal fever (MCF) virus: Ovine herpesvirus-2, the sheep-associated MCF virus
Highly fatal disease of cattle and farmed deer and occasionally pigs. Disease associated with contact with sheep, often lambing ewes, and in Africa also with wildebeest calves. Disease may occur sporadically or in outbreaks
Erosive stomatitis and gastroenteritis, erosions in the upper respiratory tract, keratoconjunctivitis, encephalitis, cutaneous exanthema and lymph node enlargement. The head and eye form is most common and there is a distinctive lesion in the cornea
Malignant catarrhal fever (MCF) is really two diseases, clinically and pathologically indistinguishable, but associated with two different infectious agents with different ecologies:
• Alcelaphine herpesvirus-1 (AHV-1) in the genus Rhadinovirus of the subfamily Gammaherpesvirinae. This is the wildebeest-associated MCF virus, transmitted to cattle from blue wildebeest (Connochaetes taurinus)
• A virus designated ovine herpesvirus-2 (OvHV-2) also a Rhadinovirus of the subfamily Gammaherpesvirinae. This is the sheep-associated MCF virus transmitted to cattle from sheep.
Neither agent appears to transmit from cattle to cattle and neither of the viruses cause any disease in their principal host, the wildebeest and the sheep. AHV-1 can be grown in eggs and tissue culture but OvHV-2 has never been propagated in vitro. The molecular genomic structure of these viruses is described.1 A gammaherpesvirus closely related to OvHV-2 has been isolated from goats2 and called caprine herpesvirus-2 (CpHV-2) and another, also closely related, has been isolated from deer3 and called deer herpesvirus (DVH). The pathogenicity of these newly recognized viruses is not known.
Wildebeest-associated MCF occurs in most African countries in cattle which commingle with clinically normal wildebeest and hartebeest. It is epizootic and seasonal. It can also occur in zoological gardens in other countries.
Sheep-associated MCF occurs worldwide. Cases mostly occur when cattle have had contact with lambing ewes and usually start 1–2 months later.4-6 Goats can also act as a source of OvHV-2 infection for cattle.7 Cases without apparent or recent exposure to sheep do occur but are uncommon.
The morbidity rate varies. Usually the disease is sporadic and presents as a single or small number of cases over a short period but on occasion up to 50% of a herd may be affected in rare but devastating outbreaks which may be short-lived or last for several months.8,9 The disease with both agents is almost invariably fatal.
Besides cattle, MCF is also an important disease of farmed deer. It is an occasional disease of pigs and is recorded in pigs that had contact with sheep on a farm and in a petting zoo.10,11
Infection with AHV-1 in wildebeest occurs in the perinatal period by horizontal and occasional intrauterine transmission, and infected young wildebeest up to the age of about 4 months have viremia and shed virus in ocular and nasal secretions. The disease is transmitted from wildebeest to cattle by contact or over short distances, probably by inhalation of aerosol or ingestion of pasture contaminated by virus excreted by young wildebeest in nasal and ocular discharges. In contrast, infected cattle do not excrete virus in nasal or ocular secretions.12 The disease can transmit between wildebeest and cattle over a distance of at least 100 m and it is suggested that cattle need to be kept at least 1 km from wildebeest to avoid disease.13
In Kenya the peak incidence of alcelaphine MCF occurs when 3- to 4-month-old wildebeest are in maximum numbers.14 In South Africa the peak incidence is at a time when young wildebeest are 8–10 months old and not infectious, requiring that there be another, high volume, source of the infection.15 The proportion of sheep in a wildebeest area which are serologically positive and presumably infected with the wildebeest-associated virus is very high.16
Virtually all domestic sheep raised under natural flock conditions are infected with OvHV-2. High rates of seropositivity have been found in domestic sheep and goats over 1 year of age in several surveys.5,17-19 In a study of 14 species of North American wildlife, a high rate of seropositivity was also found in muskox (Ovibos moschatus) and bighorn sheep (Ovis canadensis), suggesting that they might be sources of infection. There were low seropositivity rates in clinically susceptible species such as deer and bison.17
In contrast to AHV-1 infection in wildebeest, the transmission of OvHV-2 between sheep appears minimal in the perinatal period. There is no evidence for transplacental infection and although antigen, detected by PCR, is present in colostrum and milk from infected ewes, the majority of lambs are not infected until after 2–3 months of age.19,20 The rate of infection in lambs and the age at infection is not influenced by passively acquired maternal immunity and appears to be dose dependant.21,22 Infected sheep excrete OvHV-2 in nasal secretions but very high levels of excretion occur between 6 and 9 months of age, suggesting the 6 to 9-month period as the time when most virus is shed into the environment. Viral antigen has been detected in the ejaculate of rams23 but there is little epidemiological evidence for significant venereal transmission.
The means by which OvHV-2 spreads from infected sheep to cattle is not known but is presumably by inhalation or ingestion. The common epidemiological association of diseased cattle having had contact with lambing ewes suggests that perinatal lambs play a role in transmission similar to that played by wildebeest calves, however the age at infection of lambs and the excretion patterns of virus do not fit this assumption. Shedding from ewes does not increase in the lambing period.21
Contact with ewes is not a prerequisite, one outbreak having occurred when cattle commingled with rams.24 Infection can also occur when sheep and cattle are housed in the same building but with no common contact through feeding or watering points.
Occasional cases occur in cattle that have had no apparent contact with sheep and the persistence of the infection in a particular feedlot, or on a particular farm, from year to year when no contact with sheep exists, is unexplained. Persistence of the virus on inanimate fomites has been suggested but the virus is a most fragile one and this seems unlikely. The observation that some recovered cattle show a persistent viremia for many months suggests that carrier cattle may be the source of these carryover infections.12,25,26 In addition, the virus, detected by PCR, has been demonstrated in cattle and farmed deer with no evidence of MCF disease.27 It is possible that stress could activate a latent infection in animals with no sheep contact.
Sheep-associated MCF virus does not replicate in tissue culture. It has a close association with lymphoblastoid cells, particularly large granular lymphocytes, which can be grown in tissue culture, and induce MCF when injected. MCF can also be transmitted to cattle by transfusion of large volumes of blood if given within 24 h of collection. Wildebeest-associated MCF virus, can be readily transmitted by several routes. It has been adapted to grow on egg yolk-sac and tissue culture, and transmission to rabbits to yolk-sac to cattle has been achieved.
The disease shows the greatest incidence in late winter, spring and summer months. There have been suggestions that copper deficiency or exposure to bracken fern might be environmental stressors that predispose the expression of the disease in cattle.8,28
Clinical disease had been described in over 30 species of ruminants.29 In Africa assorted wild ruminants contract the disease and suffer a severe illness and a high mortality rate. Similar species in zoos are also commonly affected, e.g. Père David’s deer (Elaphurus davidianus) and Greater kudus (Strepsiceros kudu).
Amongst domestic animals, all ages, races and breeds of cattle are equally susceptible but banteng (Banteng sondaicus), buffalo (Bubalus bubalis), bison (Bison bison) and deer are more susceptible and suffer a more severe form of the disease than do commercial cattle. Disease is recorded in captive deer or farmed deer including sika deer (Cervus nippon), roe deer (Capreolus capreolus), white-tailed deer (Odocoileus virginianus), rusa deer (C. timorensis), and red deer (C. elaphus).30,31
MCF is considered one of the most important diseases of farmed deer. The clinical signs and necropsy findings closely resemble those of MCF in cattle but the morbidity and mortality can be disastrously high, resulting in heavy losses for the deer farmer.
MCF is a fatal, multisystemic disease characterized by lymphoid proliferation and infiltration, and widespread vascular epithelial and mesothelial lesions, which are morphologically associated with lymphoid cells. CD8+ T-lymphocytes are the predominant cells associated with the vascular lesions. Involvement of the vascular adventitia32 accounts for the development of gross lesions, including the epithelial erosions and keratoconjunctivitis. The lymph node enlargement is due to atypical proliferation of sinusoidal cells and the cerebromeningeal changes, usually referred to as encephalitis, are in fact a form of vasculitis. There is commonly a synovitis, especially involving tibiotarsal joints and this also is associated with a lymphoid vasculitis. It is believed that the pathogenesis of this disease is the result of direct virus–cell interactions or perhaps immune-mediated responses directed against infected cells.33
The incubation period in natural infection varies from 3–8 weeks, and after artificial infection averages 22 d (14–37 d). MCF is described as occurring in a number of forms:
4. Mild form, but these are all gradations, cases being classified on the predominant clinical signs. In serial transmissions with one strain of the virus all of these forms may be produced. The most common manifestation is the head and eye form.
There is a sudden onset of the following symptoms:
• High fever (41–41.5°C; 106–107°F)
• Rapid pulse rate (100–120/bpm)
• Profuse mucopurulent nasal discharge
• Severe dyspnea with stertor due to obstruction of the nasal cavities with exudate
• Ocular discharge with variable degrees of edema of the eyelids
Superficial necrosis is evident in the anterior nasal mucosa and on the buccal mucosa. This begins as a diffuse reddening of the mucosa, and is a consistent finding about day 19 or 20 after infection. Discrete local areas of necrosis appear on the hard palate, gums and gingivae. The mouth is painful at this time and the animal moves its jaws carefully, painfully and with a smacking sound. The mucosa as a whole is fragile and splits easily. The mouth and tongue are slippery and the mouth is hard to open. The erosive mucosal lesions may be localized or diffuse. They may occur on the:
The cheek papillae inside the mouth are hemorrhagic, especially at the tips which are later eroded. At this stage there is excessive salivation with saliva, which is ropy and bubbly, hanging from the lips. The skin of the muzzle is extensively involved, commencing with discrete patches of necrosis at the nostrils which soon coalesce causing the entire muzzle to be covered by tenacious scabs. Similar lesions may occur at the skin–horn junction of the feet, especially at the back of the pastern. The skin of the teats, vulva and scrotum in acute cases may slough off entirely upon touch or become covered with dry, tenacious scabs.
Nervous signs, particularly weakness in one leg, incoordination, a demented appearance and muscle tremor may develop very early, and nystagmus, head-pushing, paralysis and convulsions may occur in the final stages. Trismus has been described, but it is probably due to pain in the mouth rather than a neuromuscular spasm.
In natural cases the superficial lymph nodes are often visibly and usually palpably enlarged. Lymphadenopathy is also one of the earliest, most consistent, and persistent signs of the experimental disease. The consistency of the feces varies from constipation to profuse diarrhea with dysentery. In some cases there is gross hematuria with the red coloration most marked at the end of urination.
Opacity of the cornea is always present to some degree, commencing as a narrow, gray ring at the corneoscleral junction and spreading centripetally with conjunctival and episcleral hyperemia. Hypopyon is observed in some cases. In cases of longer duration, skin changes, including local papule formation with clumping of the hair into tufts over the loins and withers, may occur. In addition, eczematous weeping may result in crust formation, particularly on the perineum, around the prepuce, in the axillae and inside the thighs. Infection of the cranial sinuses may occur with pain on percussion over the area. The horns and rarely the hooves may be shed. Persistence of the fever is a characteristic of MCF, even cases that persist for several weeks with a fluctuating temperature, usually exceeding 39.5°C (103°F).
During some outbreaks an occasional animal makes an apparent recovery but usually dies 7–10 d later of acute encephalitis. In the more typical cases the illness lasts for 3–7 days and rarely up to 14 d.
In the peracute form the disease runs a short course of 1–3 d and characteristic signs and lesions of the ‘head and eye’ form do not appear. There is usually a high fever, dyspnea and an acute gastroenteritis. The alimentary tract form resembles the ‘head and eye’ form, except that there is marked diarrhea and only minor eye changes consisting of conjunctivitis rather than ophthalmia. This form of the disease has been encountered in outbreak form in cattle in large dairy herds in drylots, with only indirect contact with sheep, and in cattle to which transmission was attempted and farmed deer. A feature of this form of the disease is reported to be a brief period of slight illness followed by the final fulminating disease which is common in deer.
The mild form occurs most commonly in experimental animals but is observed in natural outbreaks. There is a transient fever and mild erosions appear on the oral and nasal mucosae. Mild disease may be followed by complete recovery, recovery with recrudescence or chronic MCF. A distinctive clinical feature in chronic MCF is persistent bilateral ocular leukomata.26
A leukopenia, commencing at first illness and progressing to a level of 3000–6000/μL has been recorded but is not a general observation. The leukopenia recorded was due mainly to an agranulocytosis. In our experience a moderate leukocytosis is more common.
Virus isolation is not practical with either virus because of the instability of cell-associated AHV-1 and the fact that OHV-2 does not replicate in cell culture. Transmission can be used for diagnosis using whole blood, nasal swabs or washings and preferably lymph node collected by biopsy, with histological lesions in the recipient rabbits or calves as the criterion. Detection of viral nucleic acid by PCR has largely replaced transmission experiments.
There are a number of serological tests that can be used but they have limited value for diagnosis of clinical cases because only a small percentage of animals seroconvert and do so late in the course of the disease. The antibody titer is low and there is cross reaction with other herpes viruses. A competitive-inhibition ELISA using a monoclonal antibody to a broadly conserved epitope of the MCF virus can be used for detection of antibody34 and has largely replaced other serological tests. It is of particular value for epidemiological studies. The development of antibody following infection is delayed in a significant proportion of young animals and serology is unreliable for determining infection status until after one year of age.
Uninfected lambs or kids under 4 months of age may test positive due to the presence of maternal antibody.
Detection of viral nucleic acid by PCR techniques is the current accepted diagnostic technique.5,27,35-37 The buffy coat is probe-positive 2 d after experimental infection with alcelaphine herpesvirus-1.37 Virus can be present in cattle without clinical MCF and if these have a disease that is not MCF, but test probe positive, a false diagnosis is possible.37
Lesions in the mouth, nasal cavities and pharynx vary from minor degrees of hemorrhage and erythema, through extensive, severe inflammation to discrete ulcers. These lesions may be shallow and almost imperceptible or deeper and covered by cheesy diphtheritic deposits. Erosion of the tips of the cheek papillae, especially at the commissures, is common. Longitudinal, shallow erosions are present in the esophagus. The mucosa of the forestomachs may exhibit erythema, or sparse hemorrhages or erosions. Similar but more extensive lesions occur in the abomasum. Catarrhal enteritis of moderate degree and swelling and ulceration of the Peyer’s patches are constant. The feces may be loose and blood stained.
Similar lesions to those in the mouth and nasal cavities are present in the trachea and sometimes in the bronchi but the lungs are not usually involved except for occasional emphysema or secondary pneumonia. The liver is swollen and severe hemorrhage may be visible in the urinary bladder. All lymph nodes are swollen, edematous and often hemorrhagic. The gross ocular lesions are as described clinically. Petechial hemorrhages and congestion may be visible in brain and meninges.
Histologically, MCF is characterized by perivascular, mononuclear cell cuffing in most organs and by degeneration and erosion of affected epithelium. The pathognomonic lesion is a necrotizing vasculitis which features infiltration of the tunica media and adventitia by lymphoblast-like cells and macrophages. Acidophilic, intracytoplasmic inclusion bodies in neurons have been described7 but their identity as viral inclusions has not been established. Large numbers of inclusion bodies have been observed in the tissue of artificially infected rabbits. The histologic features of the panophthalmitis have been described.38
Cattle with chronic MCF have chronic bilateral central stromal keratitis with or without corneal pigmentation. An obliterative arteriopathy is characteristic and this vascular lesion is present in all major organs.26 Results of a competitive inhibition ELISA serologic test suggesting a role for the virus in the development of obliterative arterial lesions in cattle5 have been supported by in-situ PCR and immunohistochemical studies of the disease in bison33 which demonstrated OHV-2 within the infiltrating lymphocytes. These lymphoblast-like cells were also shown to be CD8 (+) T-cells.
A PCR technique or immunohistochemical stains can be used to confirm the presence of viral antigen in whole blood or in tissues harvested at necropsy.35,39 When transmitted to rabbits, both the wildebeest- and sheep-associated viruses elicit a rapidly fatal lymphoproliferative disorder. The newer molecular biology-based techniques have made this bioassay method obsolete.
Treatment of affected animals is unlikely to influence the course of the disease. Non-steroidal anti-inflammatories may ease the discomfort.
Isolation of affected cattle is usually recommended but its value is questioned because of the slow rate of spread and the uncertainty regarding the mode of transmission. Because of the field observation that sheep are important in the spread of the disease, separation of cattle and sheep herds is recommended. The introduction of sheep from areas where the disease has occurred to farms with cattle should be avoided. A program to produce sheep free of OVHV-2 infection by separation and isolation of lambs before they become infected is recommended for sheep used in petting zoos.40
Attempts to immunize cattle with live or inactivated culture vaccines with Freund’s incomplete adjuvant do not provide protection against experimental challenge or natural challenge by exposure to wildebeest herds. High and persistent levels of virus-neutralizing antibody are demonstrable following vaccination but humoral mechanisms are probably not important in determining resistance to infection with the virulent virus. An inactivated wildebeest-associated MCF virus vaccine has provided protection against challenge with virulent viruses.
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