Rinderpest

Also know as: Cattle plague

Rinderpest has now been eradicated
Rinderpest is the first animal disease to have been eradicated. Small pox in humans is the only other disease that has achieved the same status. For more information see FAO website.

Introduction

Rinderpest (RV) was an acute to subacute contagious viral disease of ruminants and pigs that could cause morbidity and mortality rates in excess of ninety per cent, though inapparent infections did also occur. The disease wass characterized by necrosis and erosions in the gastrointestinal tract that resulted in severe diarrhoea and dehydration. It was 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 was 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 caused 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 was 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 excreted infectious virus in their ocular, nasal, oral and vaginal secretions and faeces. Excretion began 1 or 2 days before the onset of fever, the first clinical sign, and continued for 9 to 10 days after the start of pyrexia. Highest titres of virus were excreted during the early stages of clinical disease when epithelial lesions, especially those in the mouth, were developing to their maximum extent. Subsequently, the titres of excreted virus waned as antibody developed. Recovered cows may have aborted an infected foetus some weeks after apparent recovery, with virus excretion in their uterine and vaginal discharges.

The fragility of the virus ensured that most infectivity survived for only a few hours outside the host, though some may have persisted under favourable conditions for up to 2 to 4 days. Carcass decomposition inactivated the virus within 1 to 3 days.

Spread of RV was effected almost exclusively by contact between infected and susceptible animals. Transmission by infected aerosols probably only occured under ideal conditions of close proximity and gentle air currents, i.e. amongst housed animals. There was no carrier state in rinderpest and recovered animals did not excrete infectious RV and were not involved in the maintenance and transmission of the disease. The virus was not transmitted by arthropods and the potential for transmission through abortion was limited. Consequently, RV had a short direct cycle of infection and was spread by close contact. Under experimental conditions regular contact transmission was difficult to achieve.

In the field, rinderpest was 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 ensured good mixing of the population, especially when restricted by the availability of water during dry seasons.

In highly susceptible populations rinderpest behaved in epidemic fashion with the virus infecting virtually all susceptible individuals and causing severe clinical disease in most age groups. Endemic rinderpest, however, was much milder and was maintained by young animals usually less than 2 years old that have lost their maternal immunity. Intermediate patterns also existed.

Wildlife played an important role in rinderpest. In Asia wildlife have been described with clinical disease and such infected animals could transmit infection to other susceptible species, including domestic stock. However, the sizes and densities of wildlife populations were low and they were 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 would at first become pyrexic, dull and depressed. Signs included ulcers, vesicles and erosions on the tongue and oral mucosa, causing ptyalism, smacking of the lips and bruxism due to pain. There may also have been diarrhoea +/- blood and mucous. Diarrhoea and breath would usually have a foul odour. Generally the animal would be weak, lethargic and have a reluctance to eat. There may have been signs of weight loss or reduced weight gain and if in milk, the yield would be severely reduced. There may have been ocular signs such as excess lacrimation, blepharospasm and reddened conjunctiva. The animal may have also been in respiratory distress with dyspnoea, tachypnoea, coughing and nasal discharge all possible clinical signs.

Diagnosis

History, clinical signs and signalment/ region etc were characteristic of the disease. A presumptive diagnosis of rinderpest could be made on the basis of the clinical signs and gross pathology. However, in countries where the disease was not prevalent, and especially in regions dependent on livestock exports, it was essential to obtain laboratory confirmation of the diagnosis as soon as possible. Countries where rinderpest was either endemic or a high risk should treat any syndrome resembling rinderpest as such until proven otherwise. This would allow immediate steps to be taken to control the disease and restrict losses.

The collection of adequate quantities of appropriate specimens greatly increased the chances of an accurate laboratory diagnosis. A sample of animals in the acute stage of the disease should have been sampled. Animals that were dead, moribund or have had diarrhoea and mucopurulent discharges for more than 3 days were 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 have been 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 would 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 was to detect viral antigen using specific rabbit hyperimmune serum against RV. The most commonly used assay was the agar-gel immunodiffusion test (AGID) which was simple, easy to read, and highly specific. Counter-immunoelectrophoresis was quicker and more sensitive than AGID but required more sophisticated equipment. Immunofluorescence and immunoperoxidase staining were very sensitive but also need more equipment than AGID. Although once widely used, complement fixation and conglutinating complement absorption tests were too complicated in comparison with more recently developed tests. Various haemagglutination assays were sensitive but not yet widely applied though latex bead agglutination tests have given encouraging preliminary results and, if combined with monoclonal antibodies, may have proved 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 were negative then convalescent animals should have been 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 were 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 was under validation. During the early antibody response, serum contained significant levels of IgM to RV, the detection of which confirmed the diagnosis, though this approach was rarely used.

Histopathology was not sufficiently specific to confirm a diagnosis of rinderpest, but demonstration of syncytia and viral inclusions was supportive.

Nucleic-acid techniques including hybridization with probes and polymerase chain reactions were capable of detecting minute quantities of RV RNA in tissues and secretions, and were often a routine choice for confirmation in reference laboratories. The PCR offered 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 was 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 were 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 showed slight lymphocytosis before the onset of pyrexia. This was followed by marked lymphopenia, caused by lymphoid necrosis, which in most cases lasted throughout the acute clinical stage of the disease. During convalescence, lymphocyte levels slowly returned to normal over a period of days to weeks. The number of neutrophils remained relatively unaltered, though juvenile forms were not infrequent during the terminal stages of fatal infection. However, a degree of neutropenia that paralleled the decline in lymphocyte levels has been reported. Eosinophils may also have disappeared 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 caused haemoconcentration.

Serum aspartate transaminase and blood urea nitrogen levels increased during severe cases of disease. Serum chloride levels fell markedly in terminal illness, and other electrolytes may have been decreased in absolute terms, although this could be masked by haemoconcentration. Blood clotting may have been impaired in severely affected animals. Serum protein levels may have been 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 were a direct result of virus-induced cytopathology. Generally, the severity of the lesions was directly related to the virulence of the strain of virus involved. Complications may have arisen during convalescence through re-activation of latent pathogens, especially protozoa.

The overall appearance at necropsy was similar for most species that died of typical severe rinderpest. The carcass was dehydrated, sometimes emaciated, and usually soiled with fluid faeces. The eyes were sunken and often encrusted with mucopurulent discharge and the cheeks may have showen signs of epiphora. Erosions with or without necrotic material could be found throughout the mouth but predeliction sites were the gums, lips, buccal papillae, dorsal and ventral aspects of the tongue and the soft palate. The erosions often extended into the pharynx, anterior oesophagus, rumen (especially the pillars), the reticulum and omasum. Necrotic areas, some of which penetrated the leaves of the omasum, were sometimes present.

The folds of the abomasum were congested and oedematous and often showed necrosis, erosions and haemorrhage along the edges. The fundus of the abomasum may have had small discrete erosions that increased in size towards the pylorus where whole areas of mucosa may have become desquamated. The early necrotic lesions were pale-greyish, whereas the erosions were often red as a result of congestion of the underlying lamina propria. Haemorrhage may have occured from the raw surfaces. The abomasum was almost invariably severely affected, whereas the small intestine frequently showed less involvement. Congestion, oedema and erosions occured on the margins of mucosal folds of the anterior duodenum and terminal ileum. The Peyer's patches, being lymphoid tissue, were severely affected and swollen, dark red to almost black as a result of haemorrhage and may have sloughed completely leaving deep ulcer-like areas. Large erosions were 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 could be very striking in the colon and rectum, meriting the description ‘zebra striping’. In acute cases, the gut had little content other than desquamated necrotic epithelium, blood, and fibrin exuding from exposed lamina propria.

The urinary and gall bladders were frequently congested and haemorrhagic with occasional erosions. The vaginal mucosa may have been congested and had small erosions.

The mucosa of the upper respiratory tract, including the larynx, was congested and usually covered with mucopurulent exudate. Petechiae were frequent and necrotic, erosive lesions may have extended from the nares to the larynx. The tracheal mucosa was frequently congested. Congestion and emphysema may have been seen in the lungs, whereas secondary bronchopneumonia may have complicated chronic cases.

Although regularly described in early reports, skin lesions were recently rarely seen, although they were 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 had a predilection for lymphoid tissues, there were usually few visible changes to the superficial and visceral lymph nodes. These may have showen congestion, oedema, and a few petechiae. The nodes of animals that died after a prolonged clinical course may have bene shrunken and showed greyish radial streaks in the cortex, presumably due to haemorrhage. The spleen and haemolymph nodes appeared normal or slightly enlarged.

Histopathological lesions became more easily detectable with increasing severity of clinical disease, implying that the pathology was directly related to the ability of a strain to multiply rapidly in the tissues.

The essential histopathology of rinderpest was widespread necrosis of lymphocytes throughout the lymphoid tissues, together with syncytia and intracytoplasmic and (less frequently) intranuclear inclusion bodies. The histology in cattle was 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 were 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 were associated with the formation of syncytia and eosinophilic intracytoplasmic inclusions in the stratum spinosum. Infected epithelial cells became necrotic and slough off, leaving clearly demarcated erosions. The erosions healed rapidly unless complicated by secondary infections, which may have rarely caused them to ulcerate.

Treatment and Control

Rinderpest was a viral disease and there was no specific therapeutic treatment. Symptomatic treatment for diarrhoea and supportive antibiotic and fluid replacement therapy might conceivably have been useful in preventing the death or aiding recovery of important individual animals. However, in practice few animals were 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 did not replicate at epithelial surfaces and could not be transmitted by contact. Immunity following vaccination was complete and lifelong. The vaccine was, however, heat labile and establishment of an effective cold-chain and subsequent seromonitoring to determine the level of herd immunity were 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.

Recently, vaccination campaigns were 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 over 10 years and, as stated above, it was present in Sudan and Somalia until the 1994 Global Rinderpest Eradication Programme (GREP) succeeded in its goal in 2011.

Rinderpest Learning Resources
Flashcards Test your knowledge using flashcard type questions	Rinderpest Flashcards

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