Manual on the preparation of rinderpest contingency plans 5

Chapter 2 Nature of the disease

DEFINITION EPIDEMIOLOGICAL FEATURES Rinderpest, or cattle plague, is an acute, highly Susceptible species contagious viral disease of wild and domesti- Large domestic ruminants. Although all clo- cated ruminants and pigs. It is characterized by ven-hoofed animals are probably susceptible to sudden onset of fever, oculonasal discharges, infection, severe disease occurs most commonly necrotic stomatitis, gastroenteritis and death. in cattle, domesticated water buffaloes and yaks. In a fully susceptible population, as is the Breeds of cattle differ in their clinical response to case in non-endemic areas, morbidity and rinderpest virus. Some breeds have developed a mortality can approach 100 percent. With high innate resistance through selection by long some strains of the virus, however, the dis- association with the disease. ease may be mild with low mortality from Sheep and goats are generally less suscep- infection. tible but may develop clinical disease. Asiatic pigs are susceptible and may suffer WORLD DISTRIBUTION clinical disease. European breeds are less sus- Formerly widespread throughout Europe, Asia ceptible. The latter tend to undergo subclinical and Africa, rinderpest has now been limited to infection and play little or no part in the fairly well-defined locations in South Asia, the maintenance of the disease. Near East and eastern Africa. This has been Camels are apparently not infected and ap- achieved through various national and regional pear to have no role in rinderpest transmission rinderpest eradication programmes. Global and maintenance. rinderpest eradication, which is being targeted for 2010, is being coordinated by FAO. Wildlife. Some species, such as African buffalo, eland, giraffe, lesser kudu and warthog and Asian AETIOLOGY antelopes, bovids and swine, are highly suscep- Rinderpest virus belongs to the morbillivirus tible. Others, such as antelopes, hippopotamus genus of the paramyxovirus family. Other mem- and Indian blackbuck are less susceptible. There bers of the genus include the measles virus of is no evidence to suggest that wildlife popula- humans, the peste des petits ruminants virus of tions can maintain the disease indefinitely with- domesticated and some small wild ruminants, out concurrent disease in cattle. the canine distemper virus of dogs and wild Rinderpest does not infect humans. carnivores and the morbilliviruses of aquatic mammals. Transmission There is only one serotype of rinderpest Almost invariably, rinderpest spreads between virus, but the different strains vary in their herds and to new areas by the movement of pathogenicity. infected animals. Infected cattle start shedding 6 Nature of the disease

virus one or two days before the appearance of serve as a source of infection for pigs, which clinical signs. They continue to shed virus for may then transmit the disease to cattle. about nine to ten days after the onset of fever, and Rinderpest is not transmitted by insect vec- generally harbour the virus for no more than tors. three weeks. Infected cattle may spread virus through markets and transport it long distances Virus stability before clinical evidence of the disease is ob- At 4°C, rinderpest virus is most stable at pH values served. of 7.2 to 7.9 and is rapidly inactivated at pH less Rinderpest virus is found in expired air, than 5.6 or greater than 9.6. The virus is inacti- nasal and ocular discharges, saliva, faeces, vated rapidly at environmental temperatures by milk, semen, vaginal discharge and urine. In- solar radiation and desiccation. Pasture is infec- fection is transmitted primarily by inhalation tive for six hours if unshaded or 18 to 48 hours if of expired air contaminated by infected drop- shaded. Contaminated bare enclosures are infec- lets or by contact with secretions and excre- tive to cattle for no more than 48 hours and contami- tions from infected animals. Transmission oc- nated buildings for a maximum of 96 hours. curs mainly over short distances, but occasion- The virus is highly susceptible to many lipid- ally may occur over distances of up to 100 m or solvent disinfectants because it is enveloped. It more at night, when the effects of high tem- is also susceptible to both acid and alkaline perature and sunlight are minimal, especially conditions. It is inactivated rapidly by autoly- in conditions of very high humidity. sis and putrefaction and hence does not survive Transmission through the oral route by in- for more than 24 hours in the carcass of an gestion of contaminated feed and water is animal that has died from the disease. possible. Infected meat stored at 4°C can The virus is present in milk one or two days remain infective for at least seven days. Feed- before appearance of clinical signs. Heat treat- ing of infected meat and feed contaminated ment or pasteurization of milk is sufficient to with infective secretions and excretions may inactivate the virus.

DOMESTICATED WATER BUFFALOES The national rinderpest contingency plan should include provisions for this species, as the disease is commonly seen in buffaloes Manual on the preparation of rinderpest contingency plans 7

CLINICAL SIGNS from between three and five days to two Cattle weeks, before returning to normal. This is Rinderpest is capable, in certain situations, of accompanied by restlessness, depression, causing devastating losses in cattle herds, but inappetence and a significant fall in milk tends to have less impact in endemic areas and on yield. Respirations are shallow and rapid. partially immune populations. The disease may One or two days later, serous oculonasal dis- be peracute, acute or mild, depending on a num- charges and severe congestion of the mucous ber of factors inherent in the virus strain, the host membranes of the eyes and nose are typically and the system of management of the animals. seen. Two to five days after the onset of fever, Peracute rinderpest. In peracute rinderpest, there tiny, pinpoint greyish areas of necrosis appear is a sudden onset of fever, inappetence, depres- on the gum and lips. The lesions increase in sion, congestion of the visible mucous mem- number, enlarge and coalesce to form a thick, branes and death within two to three days, before yellow pseudo-membrane covering the oral oral erosions develop. mucosa including the lateral and ventral as- pects of the tongue. The necrotic debris easily Acute rinderpest. The OIE International animal desquamates, leaving shallow erosions with health code puts the incubation period of red layers of basal cells. Similar erosions can rinderpest as 21 days for purposes of zoosanitary also be seen on the mucous membranes of the measures. The route of infection, the dose and nose, the vulva and the vagina. Salivation is the virulence of the strain of virus may modify stimulated, the saliva being initially mucoid the incubation period. In general, the period and then mucopurulent. A distinctive foul between the first index case and the appearance odour exudes from the mouth. of secondary cases is about two weeks. Diarrhoea starts one to three days after the Typically, the disease is heralded by a sud- appearance of oral lesions. The faeces are den onset of pyrexia, which may last anything initially thin and dark in colour, and may later

A COMMON WATERING-POINT Rinderpest transmission and spread are enhanced by congregation of different herds of animals, as occurs at common watering- points 8 Nature of the disease

become watery and contain mucus, shreds of are more likely to be PPR. However, acute epithelium and specks of clotted blood. Occa- rinderpest can occasionally be seen in small sionally the liquid faeces may be red in colour. ruminants. Clinical manifestations are similar to Affected animals arch their backs and strain, those seen in cattle, and consist of fever (rectal sometimes exposing congested and eroded temperatures of 41 to 42°C), focal to coalescent rectal mucosae. necrotic stomatitis, oculonasal discharges, Respirations are laboured and painful and conjunctivitis, pneumonia and diarrhoea. there may be an audible grunt on expiration. In fatal cases the diarrhoea continues to worsen, Pigs causing rapid dehydration and visible wast- Asiatic breeds of pigs may suffer peracute or ing. Sternal recumbency follows and death acute rinderpest. Peracute disease is character- supervenes 6 to 12 days after the onset of ized by sudden onset of fever and death without fever. If animals survive, the erosions heal, further premonitory signs. Acute disease in these diarrhoea stops and a prolonged convales- breeds of pigs is manifested by sudden onset of cence follows, with recovery to full health fever, inappetence, depression, shivering, vom- taking many weeks. Pregnant cows commonly iting and epistaxis. Shallow erosions, diarrhoea, abort in the convalescent period. progressive but rapid dehydration and emacia- Skin lesions, which appear as a maculo- tion precede death. papular rash on the less hairy parts of the body such as the groin and axillae, have been de- scribed.

Mild rinderpest. The evolution and clinical signs of mild rinderpest are similar to those of the classic syndrome but are less marked. One or more of the cardinal features may be absent or only present transiently, particularly oral ero- sions, which may be meagre. Most affected cattle recover, and convalescence is short. A frequent sequel of mild infections is activation of latent pathogens, notably protozoa, occurring four to six days after the start of the prodromal fever. The signs of the activated infection may predominate and mask the appearance of clinical signs of rinderpest.

Sheep and goats Small ruminants more commonly suffer the sub- acute form of the disease, characterized by tran- sient fever without remarkable systemic distur- MILD RINDERPEST IN CATTLE bances. In areas where peste des petits ruminants One or more of the cardinal features may be absent or only present transiently, and affected animals may not (PPR) is endemic, most rinderpest-like syndromes look overtly sick Manual on the preparation of rinderpest contingency plans 9

Wildlife congestion and interlobular and alveolar em- Wild ungulates differ markedly in their manifes- physema in older cases. tation of rinderpest infection. Buffaloes react The lymph nodes in early deaths may be with a clinical syndrome essentially the same as swollen and oedematous but in late deaths that in cattle, whereas lesser kudus exhibit pro- may be shrunken and grey, with radial streaks fuse discharge of tears and corneal opacity pro- in the cortex. The spleen is usually normal but gressing to death from dehydration and starva- occasionally may have subserosal haemorrhages tion. Any unexplained incidence of morbidity along its margins. and mortality in wild ungulates in areas where there is a risk of rinderpest should be viewed with Histopathology suspicion and investigated thoroughly. Gener- Microscopic findings consist essentially of exten- ally, strains of rinderpest virus that produce mild sive lymphocytolysis with depletion of the lym- disease in cattle may cause severe disease in phocytes in the germinal centres of lymph nodes susceptible wildlife species. and the spleen. The epithelial cells of the alimen- tary tract reveal areas of necrosis and ulceration PATHOLOGY with formation of multinucleated giant cells as Gross pathology well as intranuclear and intracytoplasmic inclu- The carcass is dehydrated, sometimes emaciated sion bodies in lymphatic cells and alimentary tract and soiled with loose faeces. The eyeballs are epithelial cells. sunken and encrusted with mucopurulent dis- charges. The muzzle and external nares may be IMMUNITY encrusted with similar exudates. There is only one immunogenic type of rinderpest The oral cavity usually contains necrotic mate- virus and immunity to one strain will protect against rial and areas of erosion from desquamated epi- all other known strains. One vaccine will thus thelium, primarily on the gums, buccal papillae, protect against all field strains. Serum antibodies lateral and ventral aspects of the tongue and the are first detectable within one week of infection soft palate. In severe cases, these erosions ex- with classical rinderpest strains. However, animals tend to the pharynx, the oesophagus and the infected with mild strains may take ten days or forestomach. Lesions consisting of congestion, longer to develop neutralizing antibodies, as do oedema, haemorrhages and erosions may also be animals vaccinated with tissue-culture rinderpest seen in the abomasum and the small intestines. vaccine (TCRV). For all practical purposes, ani- The large intestines, from the caecum to the mals are immune one week after vaccination, al- rectum, may show varying degrees of conges- though serum antibody titres do not peak for about tion, erosions and linear haemorrhages (usually three weeks. Serum neutralizing antibodies are a described as zebra striping), especially around major component of active immunity against in- the ileo-caecal valve and the caecal tonsils. These fection and have an important role in recovery. haemorrhages are bright red in fresh carcasses or In endemic areas and those where vaccina- greenish-black in stale or decomposing ones. tion is routinely carried out, calves acquire The mucosa of the upper respiratory tract passive immunity with the intake of colostrum may be congested and show haemorrhages. from their immune dams and the antibody can The lungs may be normal in animals that died persist for up to 11 months, preventing vaccine in the early stages of the disease or show virus from generating an immune response. 10 Nature of the disease

DIAGNOSIS are generally lower in BMCF. Bilateral, centripetal Field diagnosis corneal opacity, accompanied by blepharospasm, Rinderpest should be suspected when there is any photophobia and hypopyon, is a feature only of unusual occurrence of morbidity associated with BMCF. However, corneal opacity is also com- a stomatitis-enteritis syndrome characterized by monly associated with rinderpest in some wildlife nasal and ocular discharge with any two of the species, especially lesser kudu. Diagnosis is con- following signs: fever, oral erosions or lesions, firmed by polymerase chain reaction (PCR) or excessive salivation, diarrhoea and death. The histopathology. mild form of rinderpest causes the most difficulty, as one or more of the characteristic features may Foot-and-mouth disease. FMD can be distin- be missing from the syndrome observed. Lesions guished from rinderpest by the presence of lame- may be limited to ocular discharge with only a ness and by the low mortality and vesicular stomatitis fleeting appearance of limited oral lesions in a in FMD as opposed to the necrotic stomatitis seen small proportion of affected calves. Only the in rinderpest. Diarrhoea, which is commonly a younger age groups may be affected, the morbid- prominent sign of rinderpest, is not a feature of ity rate may be low even in them and the mortality FMD. Diagnosis is confirmed by virus isolation rate may be so low as to be indistinguishable from and/or antigen detection. expected mortality in these age groups. Mucosal disease/bovine virus diarrhoea. BVD, Differential diagnosis usually an inapparent to relatively mild disease Epidemiological features, as well as clinical and syndrome lasting a few days, may be seen in cattle pathological signs, are highly suggestive of at any age, but particularly in calves. Morbidity is rinderpest. However, clinical signs of rinderpest usually high but mortality is generally low. MD, on may be similar to those seen in other diseases in the other hand, is a severe disease of young, grow- which fever, oculonasal discharges, stomatitis and/ ing cattle in which few animals may be affected but, or diarrhoea may be prominent features. These invariably, fatally. Differentiation of MD from include fatal mucosal disease (MD) syndrome of rinderpest is achieved by laboratory tests, includ- the bovine virus diarrhoea disease (BVD) com- ing virus isolation, immunofluorescence staining, plex, some forms of malignant catarrhal fever PCR, antigen detection or detection of rising anti- (MCF), foot-and-mouth disease (FMD), peste des body titres. petits ruminants (PPR), infectious bovine rhinotracheitis (IBR) and bovine papular stomatitis Infectious bovine rhinotracheitis. This disease (BPS). Other diseases that need to be considered in may be confused with rinderpest when diarrhoea is the differential diagnosis of rinderpest are conta- not a prominent feature of the latter. Otherwise, the gious bovine pleuropneumonia (CBPP) and East disease caused by the IBR virus is characterized Coast fever (ECF). Epidemiological features and essentially by upper respiratory symptoms. Mor- laboratory diagnostic tests are important in distin- tality rates are lower than in rinderpest. It is con- guishing between these diseases. firmed by virus isolation and/or antigen detection.

Bovine malignant catarrhal fever. Although Contagious bovine pleuropneumonia. Diarrhoea, rinderpest and BMCF resemble each other in their oral necrosis and erosions are not seen in CBPP. clinical and pathological features, morbidity rates The evolution of clinical disease is more protracted Manual on the preparation of rinderpest contingency plans 11

in CBPP because of the longer incubation period. starts towards the end of the incubation period Severe emaciation, exercise intolerance and before the appearance of clinical signs. It peaks moist, suppressed coughs are features of CBPP. during the febrile/mucosal erosion phase and Lung lesions are characteristic. then declines and stops early in the convales- cent period. East Coast fever. The presence of the tick vector Samples are best collected from animals that and absence of effective tick control, when con- are febrile and have mucosal erosions and clear sidered together with other clinical signs and the lacrymal secretions. It is generally better to col- results of microscopic examination of blood and lect samples from as many animals as possible to lymphoid tissues, are useful in the differentia- maximize the chances of positive results. tion of ECF from rinderpest. Two sets of tissue samples should be collected, one chilled and the other fixed in formol-saline. Laboratory diagnosis Those for virus isolation should be preserved in Diagnostic procedures for rinderpest and de- transport medium (phosphate buffered saline, tailed instructions on collection, preservation pH 7.6) with antibiotics and antifungals but and dispatch of samples are contained in the without glycerol, which kills the virus. FAO Manual on collection and submission of Samples for virus isolation should be trans- diagnostic specimens to the World Reference ported to the laboratory as quickly as possible, Laboratory for Rinderpest, the FAO Manual on chilled but not frozen. If storage is imperative the diagnosis of rinderpest and the OIE Manual for a period of time, samples should be kept at of standards for diagnostic tests and vaccines. -70°C (not -20°C). Laboratory confirmation of a presumptive Whole blood (without anticoagulants) should diagnosis of rinderpest may be achieved by be collected and centrifuged after clotting to tests designed to detect live virus, virus antigen, obtain the serum needed for virus antibody virus genetic materials or antibodies against detection. Serum should be stored at 4°C for the virus (in unvaccinated animals). short-term or -20°C for longer-term storage. Each sample should be put in a strong water- Collection and transport of diagnostic speci- tight primary container which is then wrapped mens. Preferred samples for virus isolation in absorbent material, placed in a strong leak- are: proof secondary container and then into a • whole (unclotted) blood collected in anti- solid outer covering. This should be labelled coagulants such as heparin or ethyl- with waterproof ink for dispatch to the na- enediamine tetra-acetic acid (EDTA); tional diagnostic, regional and/or world refer- • tissue samples from the spleen, lymph ence laboratories. Information about the car- nodes and haemolymph nodes; rier, airway bill number and flight time should • eye swabs; be sent to the laboratory ahead of dispatch. • lymph node aspirates. For the detection of virus antigen, ocular Virus isolation. Isolation of virus from lymphoid secretions, necrotic gum debris and samples tissues or blood leucocytes is done in cell cultures of the spleen, lymph nodes and tonsils should and is essential for subsequent virus character- be collected. ization and molecular epidemiological studies. Virus shedding in secretions and excretions However, the technique requires trained exper- 12 Nature of the disease

tise and aseptic tissue culture facilities, and there- RISK ASSESSMENT OF RINDERPEST fore can only be carried out in well-equipped INVASION national and specialized regional and world refer- A risk assessment of possible introduction of ence laboratories. rinderpest into the country is essential for formu- lating a national policy for rinderpest control and Antigen detection. Three techniques widely used elimination. The main risk factors to be consid- for rinderpest antigen detection and prescribed by ered include: the OIE Manual of standards for diagnostic tests • the likelihood that hidden foci of rinderpest and vaccines are the agar-gel immunodiffusion infection still remain in the country in test (AGID), the counterimmunoelectrophoresis domestic livestock or wild animals; (CIE) and the immunocapture enzyme-linked • the location and proximity of the nearest immunosorbent assay (ICE). known endemic foci; AGID and CIE detect precipitating antigens in • likely future livestock movement patterns excretions, secretions and tissue samples. ICE into the country, through trading, smuggling, may be used for definitive diagnosis and the differ- transhumance, nomadism or civil disturbances, entiation of rinderpest from PPR. particularly from rinderpest danger zones; Other techniques that may be used for anti- • the status of neighbouring countries, based gen detection include immunohistochemical not only on their rinderpest occurrences staining, immunofluorescence, electron micros- and present disease status, but also on the copy and a pen-side, monoclonal antibody- quality of their veterinary services and likely based, latex particle agglutination test which is ability to detect and control any rinderpest still under evaluation for field use. introduction; • possible socio-economic consequences of Detection of virus genetic material. Rinderpest any rinderpest introduction; virus genetic material can be detected by reverse • the difficulty of eradication if there is a transcription polymerase chain reaction (RT-PCR), breakdown. which is a very specific and sensitive technique A statement about the risk profile should be that requires specialist expertise and equipment. made expressing the probability as extreme, This technique is carried out in the collaborating high, medium or low, based on the perceived centres and world reference laboratories and in socio-economic consequences of rinderpest national laboratories that have the required exper- incursion into the country such as: tise and facilities. Nucleotide sequencing pro- • production losses; vides phylogenetic information of epidemiologi- • effect on food security and poverty alle- cal significance. viation; • restriction of livestock trade; Antibody detection. A monoclonal antibody-based • environmental effects, such as decimation and specific competitive enzyme-linked of wildlife. immunosorbent assay (ELISA) is widely used and It is necessary to identify measures that has largely replaced the virus neutralization test for would be needed to reduce these risks, such as rinderpest antibody detection. This is a robust test a ban on importation of live susceptible ani- but it cannot differentiate antibodies caused by mals from high-risk areas, and border quaran- vaccination from those caused by field virus. tine and control.