Rinderpest

Synonyms

Cattle plague.

Introduction

Rinderpest is an acute to subacute contagious viral disease of ruminants and pigs that can cause morbidity and mortality rates in excess of ninety per cent, though inapparent infections also occur. The disease is characterized by necrosis and erosions in the gastrointestinal tract that result in severe diarrhoea and dehydration. It is caused by a morbillivirus, a member of a group of enveloped viruses forming a separate genus within the family Paramyxoviridae. Viruses in this genus included rinderpest virus (RPV) infecting cattle and other large ruminants, peste des petits ruminants virus (PPRV) infecting sheep and goats, canine distemper virus (CDV) which infects carnivores, human measles virus (MV), and other members in marine mammals. Members of the genus are closely related antigenically and are distinguished from the other paramyxoviruses by their lack of neuraminidase activity.
In terms of economic losses in domestic animals, rinderpest is the most important member of the group. It was eradicated from the UK in 1877, but continued to be endemic in Africa and Asia until very recently. It was present in Sudan and Somalia until the 1994 Global Rinderpest Eradication Programme (GREP) succeeded in its goal in 2011.

Cattle and buffallo show the most severe clinical signs of Rinderpest Virus. Sheep, goats and Asiatic pigs are also susceptible and may develop clinical disease. European breeds of pig undergo subclinical infection. Infection of wild artiodactyls with strains largely maintained in cattle causes a wide spectrum of clinical disease, ranging from very severe in African buffalo (Syncerus caffer), giraffe (Giraffa camelopardalis), eland (Taurotragus oryx) and kudu (Tragelaphus strepciceros, T. imberbis) through increasingly less severe syndromes in other antelopes to mild or atypical in impala (Aepyceros melampus) and subclinical in hippopotami (Hippopotamus amphibius). There is also variation in susceptibility to clinical disease between breeds, especially cattle. Most European cattle breeds (Bos taurus) are more susceptible than Bos indicus breeds. African humpless cattle, such as the Ankole in East Africa, are notoriously susceptible in comparison to East African zebus.
Vectors and intermediate hosts are not involved in the transmission of rinderpest.

Infected animals excrete infectious virus in their ocular, nasal, oral and vaginal secretions and faeces. Excretion begins 1 or 2 days before the onset of fever, the first clinical sign, and continues for 9 to 10 days after the start of pyrexia. Highest titres of virus are excreted during the early stages of clinical disease when epithelial lesions, especially those in the mouth, are developing to their maximum extent. Subsequently, the titres of excreted virus wane as antibody develops. Recovered cows may abort an infected foetus some weeks after apparent recovery, with virus excretion in their uterine and vaginal discharges.
The fragility of the virus ensures that most infectivity survives for only a few hours outside the host, though some may persist under favourable conditions for up to 2 to 4 days. Carcass decomposition inactivates the virus within 1 to 3 days.
Spread of RV is effected almost exclusively by contact between infected and susceptible animals. Transmission by infected aerosols probably only occurs under ideal conditions of close proximity and gentle air currents, i.e. amongst housed animals. There is no carrier state in rinderpest and recovered animals do not excrete infectious RV and are not involved in the maintenance and transmission of the disease. The virus is not transmitted by arthropods and the potential for transmission through abortion is limited. Consequently, RV has a short direct cycle of infection and is spread by close contact. Under experimental conditions regular contact transmission can be difficult to achieve.
In the field, rinderpest is maintained by large, heterogeneous populations of animals with a sufficient supply of new susceptibles. In Africa in recent times the endemic areas have been those with large cattle populations belonging to nomadic or semi-nomadic people, which ensures good mixing of the population, especially when restricted by the availability of water during dry seasons. In highly susceptible populations rinderpest behaves in epidemic fashion with the virus infecting virtually all susceptible individuals and causing severe clinical disease in most age groups. Endemic rinderpest, however, is much milder and is maintained by young animals usually less than 2 years old that have lost their maternal immunity. Intermediate patterns also exist.
Wildlife play an important role in rinderpest. In Asia wildlife have been described with clinical disease and such infected animals can transmit infection to other susceptible species, including domestic stock. However, the sizes and densities of wildlife populations are low and they are not considered to be involved in the maintenance of the virus in Asia. In Africa, however, the greater population sizes and densities, the larger number of susceptible species, and the frequency with which the disease used to be reported in wildlife have lead to considerable study of rinderpest in these species. Until the 1960s a widely held view was that wildlife could maintain the virus independently of cattle, though some authorities considered cattle to be the main reservoir of infection. However, when cell-culture-attenuated vaccine led to the eradication of the disease from cattle in Maasailand [East Africa] in the early 1960s, clinical disease also disappeared from wildlife. The absence of antibodies in wildebeest and other species born after 1963 supported this and as a consequence opinion changed to the view that wildlife could not maintain the virus, which is still widely held today.

Clinical Signs

The animal will at first become pyrexic, dull and depressed. Signs include ulcers, vesicles and erosions on the tongue and oral mucosa, causing ptyalsim, smacking of the lips and bruxism due to pain. There may also be diarrhoea +/- blood and mucous. Diarrhoea and breath will usually have a foul odour. Generally the animal will be weak, lethargic and have a reluctance to eat. There may be signs of weight loss or reduced weight gain and if in milk, the yield will be severely reduced. There may be occular signs such as excess lacrimation, blepharospasm and reddened conjunctiva. The animal may also be in respiratory distress with dyspnoea, tachypnoea, coughing and nasal dishcarge all possible clinical signs.

Diagnosis

History, clinical signs and signalment/ region etc are characteristic of the disease. A presumptive diagnosis of rinderpest can be made on the basis of the clinical signs and gross pathology. However, in countries where the disease is not prevalent, and especially in regions dependent on livestock exports, it is essential to obtain laboratory confirmation of the diagnosis as soon as possible. Countries where rinderpest is either endemic or a high risk should treat any syndrome resembling rinderpest as such until proven otherwise. This will allow immediate steps to be taken to control the disease and restrict losses.
The collection of adequate quantities of appropriate specimens greatly increases the chances of an accurate laboratory diagnosis. A sample of animals in the acute stage of the disease should be sampled. Animals that are dead, moribund or have had diarrhoea and mucopurulent discharges for more than 3 days are less reliable sources of virus or antigen as the levels of these decline with the onset of antibody development. From each selected animal, whole blood should be collected for serum antibody assay, and in anti-coagulant for virus isolation from leukocytes, a biopsy from a superficial lymph node, debris from oral lesions, and ocular and nasal swabs for virus isolation and antigen or nucleic acid detection. If possible, two or more animals should be killed for necropsy examination and collection of up to three universal bottles of spleen and mesenteric lymph nodes. All specimens should be collected and bottled aseptically, kept cool on ice (but not frozen) and transported as rapidly as possible to a diagnostic laboratory. Glycerol should not be used as a preservative because it inactivates RV. The use of anti-proteases increases the survival of RV antigens in tissue suspensions and reduces the degradation of RNA.

The first procedure usually carried out is to detect viral antigen using specific rabbit hyperimmune serum against RV. The most commonly used assay is the agar-gel immunodiffusion test (AGID) which is simple, easy to read, and highly specific. Counter-immunoelectrophoresis is quicker and more sensitive than AGID but requires more sophisticated equipment. Immunofluorescence and immunoperoxidase staining are very sensitive but also need more equipment than AGID. Although once widely used, complement fixation and conglutinating complement absorption tests are too complicated in comparison with more recently developed tests. Various haemagglutination assays are sensitive but not yet widely applied though latex bead agglutination tests have given encouraging preliminary results and, if combined with monoclonal antibodies, might prove very sensitive. A positive test result in any of the tests confirms rinderpest.
The virus can be identified by inoculating sample materials into tubes containing antiserum to RV or by examining fixed monolayers using immunofluorescent or immunoperoxidase techniques.
If antigen detection and virus isolation are negative then convalescent animals should be bled again 2 to 4 weeks later. Assays for serum antibodies should demonstrate a four-fold or greater increase in antibody titre in recovered cases. Virus neutralization in microplates was most commonly used for this, although several other techniques such as measles virus haemagglutination inhibition, indirect immunofluorescence, ELISA and counter-immuno-electrophoresis are alternatives.
A number of ELISA tests have been developed. The ELISA has the advantage that laboratories without cell-culture can test thousands of sera, which is often required in current eradication programmes, and the sensitivity and specificity of these new tests is under validation at present. During the early antibody response, serum contains significant levels of IgM to RV, the detection of which confirm the diagnosis, though this approach is rarely used.
Histopathology is not sufficiently specific to confirm a diagnosis of rinderpest, but demonstration of syncytia and viral inclusions is supportive.
Nucleic-acid techniques including hybridization with probes and polymerase chain reactions are capable of detecting minute quantities of RV RNA in tissues and secretions, and are now often a routine choice for confirmation in reference laboratories. The PCR offers the advantage of providing amplified viral RNA for nucleotide sequencing in order to establish the virus sub-type or lineage for epidemiological purposes. A ‘penside’ test based, in a similar manner to tests used to confirm pregnancy in women, upon specific monoclonal antibody based latex bead agglutination is being developed for use with rinderpest.

Differentials such as mucosal disease (MD), malignant catarrhal fever, infectious bovine rhinotracheitis (particularly when caused by strains that induce diarrhoea), papular stomatitis and foot-and-mouth disease. In small ruminants, peste des petits ruminants (PPR) can resemble rinderpest.
The clinical signs and gross pathology in cattle with MD can be indistinguishable from rinderpest and diagnosis requires laboratory confirmation. However, mucosal disease usually affects very few animals in a herd, whereas morbidity rates in rinderpest are much higher. Agar-gel immunodiffusion applied to tissue suspensions can rapidly differentiate the two diseases. The differentiation of PPR from rinderpest is more difficult. Useful epidemiological evidence is provided by the absence of disease in cattle. The virus cross-reacts serologically with RV and is difficult to differentiate with hyperimmune polyclonal sera. Fortunately, contemporary studies have produced monoclonal antibodies and nucleic-acid techniques that clearly distinguish between PPR virus and RV, at least for the limited number of strains tested to date. In African countries that have previously been free of PPR it is unwise to assume that a rinderpest-like syndrome in small ruminants is not PPR.

Pathology

A proportion of infected cattle show slight lymphocytosis before the onset of pyrexia. This is followed by marked lymphopenia, caused by lymphoid necrosis, which in most cases lasts throughout the acute clinical stage of the disease. During convalescence, lymphocyte levels slowly return to normal over a period of days to weeks. The number of neutrophils remain relatively unaltered, though juvenile forms are not infrequent during the terminal stages of fatal infection. However, a degree of neutropenia that parallels the decline in lymphocyte levels has been reported. Eosinophils may also disappear from the blood during the early stages of clinical disease, returning to normal levels some 2 to 3 weeks later. In severe cases the excessive loss of water causes haemoconcentration.
Serum aspartate transaminase and blood urea nitrogen levels increase during severe cases of disease. Serum chloride levels fall markedly in terminal illness, and other electrolytes may decrease in absolute terms, although this can be masked by haemoconcentration. Blood clotting may be impaired in severely affected animals. Serum protein levels may be lowered, especially in fatally infected animals. In cattle recovering from experimental infections a rise in serum globulins was attributed to the specific humoral response to the virus, but since the challenge material was citrated blood this may need re-interpretation in the light of known responses to heterologous tissue antigens.
The lesions of rinderpest are a direct result of virus-induced cytopathology. Generally, the severity of the lesions is directly related to the virulence of the strain of virus involved. Complications may arise during convalescence through re-activation of latent pathogens, especially protozoa.
The overall appearance at necropsy is similar for most species that die of typical severe rinderpest. The carcass is dehydrated, sometimes emaciated, and usually soiled with fluid faeces. The eyes are sunken and often encrusted with mucopurulent discharge and the cheeks may show signs of epiphora. Erosions with or without necrotic material may be found throughout the mouth but predeliction sites are the gums, lips, buccal papillae, dorsal and ventral aspects of the tongue and the soft palate. The erosions often extend into the pharynx, anterior oesophagus, rumen (especially the pillars), the reticulum and omasum. Necrotic areas, some of which may penetrate the leaves of the omasum, are sometimes present.
The folds of the abomasum are congested and oedematous and often show necrosis, erosions and haemorrhage along the edges. The fundus of the abomasum may have small discrete erosions that increase in size towards the pylorus where whole areas of mucosa may become desquamated. The early necrotic lesions are pale-greyish, whereas the erosions are often red as a result of congestion of the underlying lamina propria. Haemorrhage may occur from the raw surfaces. The abomasum is almost invariably severely affected, whereas the small intestine frequently shows less involvement. Congestion, oedema and erosions may occur on the margins of mucosal folds of the anterior duodenum and terminal ileum. The Peyer's patches, being lymphoid tissue, are severely affected and are swollen, dark red to almost black as a result of haemorrhage and may slough completely leaving deep ulcer-like areas. Large erosions are commonly found on the ileocaecal valve. In the large intestine, marked oedema and congestion accompanied by petechiae or larger haemorrhages occur, particularly along the crests of longitudinal folds of the mucosa. This can be very striking in the colon and rectum, meriting the description ‘zebra striping’. In acute cases, the gut has little content other than desquamated necrotic epithelium, blood, and fibrin exuding from exposed lamina propria.
The urinary and gall bladders are frequently congested and haemorrhagic with occasional erosions. The vaginal mucosa may be congested and have small erosions.
The mucosa of the upper respiratory tract, including the larynx, is congested and usually covered with mucopurulent exudate. Petechiae are frequent and necrotic, erosive lesions may extend from the nares to the larynx. The tracheal mucosa is frequently congested. Congestion and emphysema may be seen in the lungs, whereas secondary bronchopneumonia may complicate chronic cases.
Although regularly described in early reports, skin lesions are now rarely seen, although they are reputedly common in domestic buffalo. The exudative dermatitis would seem to develop from macular to pustular lesions, but the role of secondary bacterial infections such as Dermatophilus congolensis needs clarification.
Although RV has a predilection for lymphoid tissues, there are usually few visible changes to the superficial and visceral lymph nodes. These may show congestion, oedema, and a few petechiae. The nodes of animals that die after a prolonged clinical course may be shrunken and may show greyish radial streaks in the cortex, presumably due to haemorrhage. The spleen and haemolymph nodes appear normal or slightly enlarged.
Histopathological lesions become more easily detectable with increasing severity of clinical disease, implying that the pathology is directly related to the ability of a strain to multiply rapidly in the tissues.
The essential histopathology of rinderpest is widespread necrosis of lymphocytes throughout the lymphoid tissues, together with syncytia and intracytoplasmic and (less frequently) intranuclear inclusion bodies. The histology in cattle is similar with lytic destruction of lymphoid tissues, especially germinal centres, sometimes accompanied by an increase in the numbers of macrophages. In acute cases lymph nodes are virtually devoid of cells, with just a reticular stroma containing eosinophilic material remaining.
The early epithelial lesions in the squamous epithelium of the digestive tract are associated with the formation of syncytia and eosinophilic intracytoplasmic inclusions in the stratum spinosum. Infected epithelial cells become necrotic and slough off, leaving clearly demarcated erosions. The erosions heal rapidly unless complicated by secondary infections, which may rarely cause them to ulcerate.

Treatment and Control

Rinderpest is a viral disease and there is no specific therapeutic treatment. Symptomatic treatment for diarrhoea and supportive antibiotic and fluid replacement therapy might conceivably be useful in preventing the death or aiding recovery of important individual animals. However, in practice few animals are treated.

The development of live attenuated vaccines against morbillivirus diseases was the key to achieving effective vaccination, because the immunity they generate is long lived and involves a cell-mediated immune response. In the early 1960s a cell-culture-attenuated vaccine was introduced which was completely safe and relatively easy to produce and induced no clinical signs following inoculation into domestic animals. In addition, the virus does not replicate at epithelial surfaces and cannot be transmitted by contact. Immunity following vaccination is complete and lifelong. The vaccine is, however, heat labile and establishment of an effective cold-chain and subsequent seromonitoring to determine the level of herd immunity are essential prerequisites for a successful vaccination campaign. Improvements in freeze-drying techniques have greatly increased the stability of the vaccine in the dry form but it is still very labile when reconstituted and, like MV vaccine, must be used within a very short period.
Currently, vaccination campaigns are underway in Africa (Pan African Rinderpest Campaign or PARC), West Asia (WAREC) and South Asia (SAREC) in an attempt to eradicate the disease globally by the year 2010. Rinderpest has not been reported from West or Central Africa for 10 years and, as stated above, the disease is now confined to two most insecure areas of eastern Africa.

References

OIE Handistatus, 2004. World Animal Health Publication and Handistatus II (data set for 2003). Paris, France: Office International des Epizooties.
OIE, 2009. World Animal Health Information Database - Version: 1.4. World Animal Health Information Database. Paris, France: World Organisation for Animal Health. http://www.oie.int

Links to Websites

Website URL Comment Office International des Epizooties http://www.oie.int FAO -EMPRES http://www.fao.org/ag/AGA/AGAH/EMPRES/index.asp Information about the FAO initiative, Emergency Prevention System against transboundary animal and plant pests and diseases (EMPRES). Institute for Animal Health http://www.iah.bbsrc.ac.uk