Rinderpest

Vet Clin Food Anim 18 (2002) 515–547

Rinderpest Peter L. Roeder, BvetMed, MSc, PhDa,*, William P. Taylor, BVM&S, BSc, PhDb a

Animal Health Service, FAO, Vialle delle Terme di Caracalla, 00100, Rome, Italy b Beach Crescent, South Terrace, Littlehampton, West Sussex BN17 5NT, UK

The historical impact of rinderpest was explained in graphic terms by Scott and Provost [1]. They described it as the most dreaded bovine plague known, belong[ing] to a select group of notorious infectious diseases that have changed the course of history. From its homeland around the Caspian Basin, rinderpest, century after century, swept west over and around Europe and east over and around Asia with every marauding army, causing the disaster, death and devastation that preceded the fall of the Roman Empire, the conquest of Christian Europe by Charlemagne, the French Revolution, the impoverishment of Russia and the colonization of Africa.

Rinderpest, also referred to commonly as cattle plague in severe, epidemic form, is a serious contagious disease of cattle, Asian buffaloes, yaks, and many other artiodactyls, both domesticated and wild, including swine, African buffaloes, and giraffes. Although rinderpest never took hold in either the Americas or in Australia–New Zealand, it always has been a disease that attracts universal fear through its ability to lay waste to a farming community. During the first half of the twentieth century, the consistent application of zoosanitary and prophylactic measures greatly reduced the extent of the disease so that by 1960, it had been eradicated from Europe, Russia, China, and the Far East but remained entrenched on the Indian subcontinent and in those African countries immediately south of the Saharan desert. In 1992, to alter this situation, the Food and Agriculture Organization (FAO) of the United Nations proposed a technical partnership involving national veterinary authorities in all remaining rinderpest-affected countries, thereby setting the scene for the development of the Global Rinderpest Eradication Programme

* Corresponding author. E-mail address: [email protected] (P.L. Roeder). 0749-0720/02/$ - see front matter
2002, Elsevier Science (USA). All rights reserved. PII: S 0 7 4 9 - 0 7 2 0 ( 0 2 ) 0 0 0 3 5 - X

516

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

(GREP), which now aims to achieve the eradication of rinderpest by the year 2010. Although there are many sound reasons for pursuing this objective, not least to improve the profitability of livestock keeping and livestock trading, above all else the elimination of rinderpest will benefit rural food security and livelihoods in many developing countries; for this final reason, it must succeed.

The virus Rinderpest is caused by a member of the Morbillivirus subgroup of the Paramyxoviridae. Other members to which it is related closely are the viruses of peste des petits ruminants, canine distemper, measles, phocine distemper, and cetacean distemper [2]. In taxonomic terms, all natural hosts fall within the order Artiodactyla (two- or four-toed mammals) and include members of the families Bovidae, Camelidae, and Suidae, that is, domestic cattle, domestic buffalo, yaks, sheep, goats, pigs, camels, and a large number of wildlife species. Rabbits can be infected experimentally, and suroks and susliks (rodents of the genera Marmuta and Citellus, respectively) also have been proposed on the same basis as potential hosts in the Russian Far East (Sergei Starov DVS, PhD, Vladimir, Russia, personal communication, June 1999). A related morbillivirus from English hedgehogs (Erinaceus europaeus) has been described [3], and another may be present in American cattle [4]. Rinderpest virus was most likely the progenitor of human measles virus [2,5] some 10,000 to 15,000 years ago during domestication of cattle in Asia [6]. Rinderpest virus is relatively labile in adverse environmental conditions and survives best at low or high relative humidities. It is sensitive to heat, light, and ultrasound. High and low pH levels denature the virus; consequently, rinderpest-infected carcasses are rendered safe relatively quickly by the fall in pH that follows autolysis and putrefaction, together with the inactivating effect of high ambient temperatures. Being enveloped, rinderpest virus is destroyed by lipid solvents; lipophilic disinfectants are recommended for cleansing contaminated premises. In the presence of organic matter, the most effective disinfectants are 5% sodium hydroxide and 50% carbolic acid (Lysol) [7]. Glycerol also destroys rinderpest virus and must not be used in transport media.

The existence of different lineages of rinderpest virus and their epidemiologic significance In recent years, nucleic acid sequencing has contributed enormously to the ability to compare the genetic structure of different rinderpest isolates and relate them in the form of a phylogenetic tree (Fig. 1). The technique groups strains according to their evolutionary divergence and provides a

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

517

Fig. 1. Rinderpest phylogeny as illustrated by a dendrogram depicting the ‘‘family tree’’ of virus sequences contained in the FAO World Reference Laboratory for Rinderpest database. Viruses are identified by their country and year of detection. GTV ¼ goat tissue–culture vaccine; RBOK ¼ tissue-culture rinderpest vaccine. (Modified from data provided by T. Barrett BSc, MSc, PhD, of the Institute for Animal Health, Pirbright Laboratory, United Kingdom; with permission.)

basis for determining the relationships and epidemiologic significance of contemporary strains. Using all available historical strains of rinderpest, practitioners now have a sequence database that splits wild-type rinderpest virus into three distinctive lineages, two that occurred in Africa and one from Asia [8]. It should be stressed that the three lineages are related closely antigenically and do not represent subtypes of the virus. The fact that the virus has diverged at all, however, suggests that in addition to virulence,other selection pressures occasionally have been active, causing the

518

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

virus to change. The fact that there are only three lineages suggests that such pressures are exerted infrequently. A brief history of rinderpest Until recently, rinderpest was regarded as the most dangerous of all pathogens of cattle and domestic buffaloes, because its repeatedly demonstrated ability to kill large numbers of these animals strikes at the very heart of the livestock industry in countries where the disease exists. The virus has a number of characteristics, however—single serotype, close contact required for spread, no carrier state, long duration of immunity—that have allowed State Veterinary Services to progressively reduce the extent of the virus’ geographic distribution. Virtually the entire history of rinderpest, which certainly traces back to the Middle Ages, took place on the land mass made up of Europe, Russia, the Far East, the Indian subcontinent (India and Pakistan), the Middle East, and the Arabian peninsula. In Russia, after a long history of affliction, as recently as 1884 the virus was killing more than a million animals annually. A turning point was reached in 1879 with the enactment of stringent zoosanitary legislation allowing for the immediate slaughter of affected animals. These measures are credited with the eradication of rinderpest from European Russia by 1908. Zoosanitary methods continued to play a large part in the eradication of rinderpest from the whole of Russia by 1928. Europe has been essentially rinderpest-free for virtually a century. Outbreaks such as those experienced in Belgium in 1920 and Italy in 1949 were introduced in cattle and wildlife imported from India and Somalia, respectively. Interestingly, it was the Belgian incident that led to the only introduction of rinderpest into the Americas. Cattle infected in Belgium were shipped to Brazil and introduced rinderpest; fortunately, this outbreak was eliminated rapidly. The most recent outbreak in Europe was in Georgia in 1989 and 1990, caused by a virus closely related to the vaccine strain in use at the time; reversion to virulence is the most likely explanation. A ‘‘Near East’’ pandemic of rinderpest that swept from Afghanistan through Iran to the Mediterranean littoral and into the Arabian peninsula in the late 1960s to early 1970s left pockets of infection in several countries. Occasionally reinforced by reintroductions through livestock trade, these effects lingered on until 1996 to 1997, despite the efforts of a West Asian Rinderpest Eradication Campaign, which functioned from 1989 to 1994. China, in which rinderpest outlived the disease in Russia by some 20 years, initiated a rinderpest eradication program in 1948. At that time, the losses of cattle, buffaloes, and yaks exceeded one million annually, and it was noted that there could be no agricultural development until eradication had been accomplished. An intensive vaccination program was the method of choice, yet early live vaccines retained unacceptable virulence for some breeds of Chinese cattle, especially for yaks. It became feasible, however,

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

519

with development of a live goat- and sheep-attenuated vaccine from the Japanese lapinized vaccine virus made from lymph nodes, spleens, and blood of affected animals. After intensive vaccination campaigns of short duration (1950–1955), no outbreak has occurred since 1955 (Professor Shen Rongxian, China, personal communication, October 1997). This situation is an example of one in which a strong vaccination program can rapidly diminish the incidence level to zero. India launched a similar campaign in 1956 based on the availability of goat-attenuated vaccine, later replaced by tissue culture–attenuated vaccine. The stated aim of the campaign was to vaccinate 80% of the population in as short a time as possible, but in a number of states, it took up to 8 years before uptake figures equaled this proportion of the population, by which time some of the earlier vaccinates presumably had died of old age. In contrast with the Chinese experience, these campaigns failed to reduce the rinderpest incidence to zero, although a good measure of control was achieved in some states. Into the 1980s, rinderpest persisted in a number of states, and although vaccination campaigns continued, they largely had become institutionalized and ineffectual. Between 1992 and 1995, a European Union–Government of India partnership program succeeded in eradicating the virus. The main thrust of this program was to determine areas of residual endemicity, to end vaccination in rinderpest-free areas, and to reconcentrate its use in areas still harboring the virus. A parallel program in Pakistan has replaced routine rinderpest vaccination with a vaccine bank facility and a plan to ring vaccinate around confirmed outbreaks. With no outbreaks reported since September of 2000, the Asiatic lineage must be either close to extinction or already eliminated. Although the virus was being constrained on the Eurasian landmass, its range was being extended by invasion of another one. Toward the end of the nineteenth century and again at the start of the twentieth century, the virus was introduced into Africa. After a massive pandemic, the end result was the establishment of endemic disease throughout the pastoral areas of subSaharan Africa in eastern, central, and western Africa and repeated epidemics in contiguous agropastoral and sedentary populations. Freeing Africa from rinderpest has proved difficult to achieve, and although successes can be reported, so can failures. Although some of these failures can be attributed to the aid-dependency situation in which a number of the State Veterinary Services now find themselves, it also is becoming clear that issues relating to a basic understanding of factors modulating the virulence of the virus are still not understood. In Africa, coordinated vaccination programs have worked well to control the disease but not yet to eliminate it from the continent. Joint Project 15, mounted in the 1960s and 1970s, rapidly suppressed the disease with the Organization of African Unity as coordinator and with the assistance of many international organizations, donors, and national governments. The apparent clearance of rinderpest from large parts of Africa and expectations

520

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

of its eventual demise if vaccination were continued led to complacency and a failure to seek a more dynamic approach in the final stages of the campaign. In hindsight, it is easy to see that the residual reservoirs of infection left in the Senegal River basin and in the Greater Horn of Africa were the source of rinderpest resurgence once disease-control efforts waned with the phasing out of donor support. It is unfortunate that this situation occurred at the same time that Nigeria’s economic strength was in ascendancy. Nigerian wealth created a high demand for beef that was met by cattle traders supplying from as far away as the Sudan and Ethiopia and Mauritania. The inevitable reinvasion of the countries freed from disease during the previous decades constituted the second Great African Rinderpest Pandemic of the late 1970s and early 1980s, when viruses from east and west met in Nigeria, devastating livestock herders’ lives. In retrospect, it is also clear that failure to strengthen disease-reporting systems led to a serious under-reporting of rinderpest outbreaks, even in West African countries from which the disease generally was believed to have been eliminated. The emerging problem was not recognized until the pandemic was already well established. This second African pandemic was a cause of great concern for the international community and the livestock owners of affected countries. The FAO provided assistance for many affected countries and worked with the Organization of African Unity Inter-African Bureau of Animal Resources and donors to organize a fresh campaign. By 1986, when the Pan-African Rinderpest Campaign (PARC) began operations, rinderpest distribution again had been reduced greatly. In West Africa, rinderpest was last seen on the border between Ghana and Burkina Faso in 1988. PARC now has been replaced by a third internationally coordinated program, the Pan-African Programme for the Control of Epizootics, which, among other things, aims to bring about the final eradication of rinderpest from the continent. At the present time, West Africa is still free from infection. Elsewhere, the virus is confined to two reservoirs. In southern Sudan (African lineage 1), it now seems highly vulnerable. At the time of this writing in mid-2000, there is reason for cautious optimism that this reservoir might have been eliminated in the past year; this expectation now needs to be proven by intensive surveillance. In East Africa, however, the virus (African lineage 2) present in the southern Somali pastoral ecosystem has lost, probably temporarily, most of its virulence for cattle but not for wild animals, particularly African buffaloes (Syncerus caffer). Because it is unlikely that the virus will die out spontaneously, its hidden presence poses a grave risk for the rest of the continent, the more so in view of the winding down of successful vaccination campaigns where the virus has been eliminated. Although it still would succumb to intensive vaccination, the issue is one of finding both the will and the means to define its geographic distribution. Given that this distribution seems not definable on the basis of clinical reporting, planning and implementing the use of vaccination and zoosanitary procedures to remove rinderpest from the Somali pastoralists’ herds poses a major problem.

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

521

Since 1992, the international coordination of rinderpest eradication has been undertaken through the GREP supported by the FAO. Clinical and serologic surveillance data are accumulating in testimony to the absence of rinderpest from all areas except the known or suspected reservoirs of infection. Fig. 2 illustrates the progressive clearance of rinderpest, culminating in the current situation, in which the virus is maintained in no more than two reservoirs: one in the Indus River buffalo tract of Pakistan, possibly already eliminated, and the other in the Somali pastoral ecosystem of southern Somalia and northern Kenya. The disease Until recently, rinderpest was regarded as the most dangerous of all the pathogens of cattle, domestic buffaloes, and yaks because its frequently demonstrated ability to kill these animals in large numbers struck at the very heart of attempts to modernize the livestock industry of countries where the disease existed. The relief from this threat afforded by successful national eradication programs and secured by incorporating them in a global program cannot yet be taken entirely for granted. The clinical and pathologic aspects of the disease were reviewed extensively by Rossiter [9]. The most comprehensive description of rinderpest is that given by Curasson [10], but most of the description is misleadingly dramatic, having been based on virgin-soil epidemics. For centuries, the descriptions of rinderpest have portrayed a severe disease with signs varying among peracute, acute, or subacute and generally associated with a group of constant and characteristic clinical signs. Only lately have practitioners come to appreciate fully the genetically controlled variations in viral

Fig. 2. Maps demonstrating progress in clearance of rinderpest during the past 20 years; the probable situation in 2002 requires confirmation.

522

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

virulence and that at least one successful strain of the virus exists currently in which clinical manifestations can be difficult to observe. Classic cattle plague is increasingly a rare event last experienced in northern Pakistan in 1994 to 1995. Indeed, mild rinderpest, in which the disease is less dramatic and less typical, often with one or more of the cardinal features lacking, may well be the more normal situation, especially in highly endemic areas and in populations with some inherited resistance. Therefore, when considering the evidence that rinderpest is no longer circulating in a hitherto infected country, it is important to realize that such a conclusion is unjustifiable on clinical grounds alone. The acute and subacute forms of the disease in cattle and buffaloes The following clinical account is based on the likely appearance of the disease in wholly susceptible breeds of unhumped cattle (Bos taurus), water buffalo (Bubalus bubalis), and yaks (Bos grunniens); it easily might be less severe in humped zebu cattle (Bos indicus). Probably not every affected animal will show all of the different rinderpest signs, but if a group of animals is involved, and if they are all examined thoroughly, in total all the signs will be seen and as soon as mouth lesions are observed, there should be no hesitation in suspecting rinderpest. Animals that develop clinical rinderpest do so only after being in contact with a previously infected animal. The incubation period between this contact and the appearance of the first signs of the disease is usually between 8 and 11 days. At the end of the incubation period, the infected animal develops a fever usually lasting between 6 and 8 days. Measured from the outset, the temperature of affected individuals climbs steadily during the first 2 to 4 days, from normal to between 40C to 41.2C (104F–106.2F). During this phase of the disease, the animal is obviously sick, but no diagnosis can be made. In addition to pyrexia, the other signs that may be noted at this time include constipation; partial anorexia; congestion of visible mucus membranes (especially the conjunctiva); the development of clear, serous ocular and nasal discharges; depression; drop in milk yield; and drying of the muzzle. This introductory or prodromal period lasts between 3 and 4 days, and during it an increasing proportion of affected animals are infectious for other susceptible animals [11], the virus being shed in nasal, ocular, and oral secretions and in the feces. It is assumed that if a veterinarian is called to an animal in the prodromal phase of rinderpest he or she will recognize the fact that the animal is ill, probably seriously so. Assuming that the sick animal or animals then would be inspected on a daily basis, there should be no difficulty in quickly reaching a clinical diagnosis of rinderpest. Within 4 to 5 days of the onset of pyrexia, practically all affected animals move into the erosive phase, which is characterized by the development of necrotic mouth lesions typical of rinderpest and that lasts a further 4 to 5 days. Initially, small, pinhead-sized

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

523

flecks of slightly raised, whitish, necrotic epithelium make their appearance on the lower lip and gum. During the next 1 or 2 days, similar lesions probably will appear on the margin between the upper gum and the dental pad, on the underside of the free portion of the tongue, on the floor of the mouth adjacent to the lingual carunculae, on the cheeks and cheek papillae, and on the hard palate. In addition to the appearance of fresh foci, previously existing ones enlarge and coalesce so that from one day to the next, the distribution and extent of the necrotic epithelial lesions increase dramatically. Because of the movements of the tongue, much of this necrotic material detaches to leave shallow, nonhemorrhagic erosions (Fig. 3). In severe cases the entire oral epithelium becomes involved, and considerable erosion takes place. Excess salivation often is seen. Most affected animals develop diarrhea 1 to 2 days after the onset of oral necrosis. The diarrhea is usually copious and watery at first and may be expelled violently, as so-called ‘‘shooting diarrhea.’’ Later on it may contain mucus, blood, and shreds of epithelium and its passage may be accompanied by severe straining. During this period, the general signs become increasingly severe. The animal will be completely anorexic, thirsty, restless, and depressed; the muzzle dries out completely and may desquamate. Necrosis of the mucus membrane of the nasal vestibule, the vulva, vagina, and preputial sheath may be observed. The ocular and nasal discharges become mucopurulent, and the breath becomes fetid (Fig. 4). On an individual basis, the outcome of the infection is determined late in the erosive phase of the disease. Animals without sufficient resistance may collapse and die within a matter of hours, frequently showing abnormally

Fig. 3. Classic erosions on the dental pad, gums, and cheek papillae. (Courtesy of R. Heinonen, DVM, MSc.)

524

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

Fig. 4. Mucopurulent ocular and nasal discharges and excess salivation. (Courtesy of Peter L. Roeder, BVetMed, MSc, PhD.)

low body temperatures before they do so. Others become recumbent for 1 or 2 days before death. In fatal cases, the diarrhea worsens progressively, causing rapid dehydration. Affected animals waste visibly; they have sunken eyes and stand with lowered heads and arched backs. Most collapse and die 6 to 12 days after the onset of the prodromal phase, but some may linger for 3 weeks. Overall, if the attack is an acute one, up to 70% of the cases may die. In animals that go on to recover, the pyrexia may remit slightly in the middle of the erosive period and then, 2 to 3 days later, return rapidly to normal. At the same time the mouth lesions resolve rapidly, the diarrhea ceases, appetite returns, and an uncomplicated convalescence ensues. To some extent, the virulence of the virus seems to be tempered by transmission opportunities, and in largely susceptible populations it gains in virulence. The picture described in the preceding paragraphs typifies what happens when the infection enters a farm made up entirely of susceptible animals or a district where no prophylactic vaccination has been undertaken. On the other hand, in areas of long-standing endemicity in which a partially immune population exists owing to either vaccination or to previous exposure to infection, although acute cases still may be found, the morbidity rate and virulence of the virus probably will seem to be reduced. Under these circumstances, the disease runs the same overall course, but clinically the disease has become subacute. The extent to which mouth lesions, diarrhea, and the various other signs develop will be less dramatic, and the case-fatality rate may be much lower (typically 5%–10%). Abortion is a common sequel to infection of pregnant cows [12]. Destruction of lymphocytes by rinderpest virus results in a marked lymphocytopenia lasting for several weeks in both acute and subacute disease. The resulting immunosuppression encourages microbial superinfection and reactivation of a number of latent infections, such as hemoprotozoa and

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

525

intestinal coccidia. The clinical signs tend to mask those of rinderpest and cause diagnostic confusion. The peracute form of the disease in cattle Exceptionally, a strain can increase in virulence to such an extent that the resultant infection leads to the host’s death during the prodromal phase of the infection. Effectively, the clinician would be faced with cattle showing depression, anorexia, a rapidly climbing body temperature, and sudden death. In these circumstances, although a diagnosis would require laboratory assistance, few viruses apart from rinderpest have the potential to inflict such havoc in a herd. The mild form of the disease in cattle Although it is poorly understood, a natural selection pressure favoring the emergence of virtually avirulent strains of rinderpest seems to exist. Probably derived from strains causing subacute rinderpest, the result is a virus that can cause a virtually silent infection in a humped ox and a very low-grade infection in a European breed. Such strains—and the disease they cause—are termed mild. There has been a tendency to equate reduced virulence with African lineage 2 rinderpest virus, but this association is a mistake because mildness is a common feature that has been observed with all three lineages of the virus. For example, in addition to recent isolates of African lineage 2 from East Africa, African lineage 1 in Egypt in the early 1980s [13] and Kenya [14,15] and Asian lineage 3 virus in northern Iraq in 1995 all caused mild disease; in contrast, the RGK/1 strain of African lineage 2 virus is fully virulent for cattle [14]. Mild rinderpest can be difficult to diagnose clinically because of the reduction in the intensity of clinical signs and the shorter time during which they are present. Generally mild strains cause a relatively low pyrexia of 3 to 7 days’ duration, but at the same time, a proportion of the infected animals completely fails to react. The same can be said of the appearance of mouth lesions and other signs. Mouth lesions tend to be of a limited nature, sometimes no more than a single or small number of pinpoint flecks of necrosis on the upper or lower gum, lasting no more than 1 to 2 days. One of the difficulties in diagnosing mild cases is that most infected animals do not lose their appetite or become depressed. With these conditions, field diagnosis is less than easy, and routine surveillance operations probably would fail to recognize the presence of such a virus. It seems that when combined with intercurrent stress, however, the clinical picture more closely resembles that of subacute rinderpest, and a clinical diagnosis is made easier. Rinderpest in other domestic animals Pigs are susceptible to rinderpest. In India, outbreaks have been reported in both scavenging village pigs [16] and in improved pigs [17]. Both types

526

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

showed pyrexia, conjunctivitis, profuse lachrymation, buccal ulcers, and diarrhea; deaths were reported. Sheep and goats are susceptible to infection. African breeds seem to be clinically resistant to infection with African strains. In India, small ruminants undoubtedly showed clinical signs when infected with Indian strains, but the widespread presence of peste des petits ruminants virus at village level reduced the value of the evidence that these species were involved in maintaining rinderpest [18]. Camels are susceptible to rinderpest but develop an inapparent infection that they do not transmit [19]; in an endemic area, they may undergo natural infection [20]. Rinderpest in wildlife Rinderpest has been reported to cause severe disease in many species of wildlife in Africa. A broad range of wild ungulates are, to some degree, susceptible to rinderpest infection, yet frank clinical disease is seen most frequently in only a relatively limited number of animals. Most commonly, these animals are African buffaloes (Syncerus caffer), lesser kudu (Tragelaphus imberbis), eland (Taurotragus oryx), and giraffe (Giraffa camelopardalis), with warthog (Phacochoerus sp) and wildebeest (Connochaetes Taurus) sometimes involved. There seem to be differences between virus strains determining which species are affected, but the affinity can change during the course of an epidemic. Wildlife are extremely valuable indicators of mild rinderpest virus infection transmitting in cattle with which they are in contact. A similar situation existed in Asia in the past. Infection and classic disease have been recorded as occurring in many ungulate and porcine species, including Indian ‘‘bison’’ or gaur (Bos gaurus) [21]; Indian Axis deer (Axis axis) [22]; numerous species of wild pigs and ruminants in southeast Asia, including banteng (Bos javanicus) and gaur but interestingly, not kouprey (Novibos sauveli) [23,24]; and the Mongolian gazelle (Procapra gutturosa) and Saiga antelope (Saiga tatarica) of the Central Asian steppe [25]. High mortality is to be expected in African buffaloes in which the disease, as in eland and kudu, closely resembles classic disease in cattle [26]. Ocular lesions predominate in lesser kudus and giraffe and have been encountered in buffaloes [27]. In addition to corneal opacity, the lesions extend to keratoconjunctivitis, uveitis, and cataract. Kock et al [27] also described tenosynovitis of the limb joints in kudus and cutaneous lesions in buffaloes. Gross pathology Typically, the carcass is dehydrated, emaciated, and soiled. The nose and cheeks usually bear evidence of mucopurulent discharges, the eye is sunken, and the conjunctiva congested. In the oral cavity, there is often extensive desquamation of necrotic epithelium, which always appears sharply demarcated from adjacent areas of healthy mucosa. The lesions frequently extend

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

527

onto the soft palate and also may involve the pharynx and the upper portion of the esophagus; the rumen, reticulum, and omasum usually are unaffected, although necrotic plaques occasionally are encountered on the ruminal pillars. The abomasum, especially the pyloric region, is affected severely and shows congestion, petechiation, and edema of the submucosa. Epithelial necrosis gives the mucous membrane a slate-like color. The small intestine is not commonly involved, except for striking changes to the Peyer’s patches, where lymphoid necrosis and sloughing leave the supporting architecture engorged or blackened. In the large intestine, changes involve the ileocecal valve, the cecal tonsil, and the crests of the longitudinal folds of the cecal, colonic, and rectal mucosae. The folds appear highly engorged in acute deaths or darkly discolored in long-standing cases; in either event, the lesions are referred to as zebra striping. The lungs are usually normal, but the trachea and major bronchi may show severe engorgement and in protracted cases that have been recumbent for some time, bullous and interstitial emphysema may be seen. Epidemiologic features of rinderpest Transmission Rinderpest spreads when healthy, susceptible animals are exposed to infected aerosols either in the breath of a sick animal or in its virus-rich secretions or excretions. Droplets are large and short-lived, so the contact must be close for transmission to occur. Only rarely does infection transmit over more than a few meters or by other means. A rare exception was infection of swine by ingestion of meat scraps from infected animals, which was believed to have played a role in the transmission of rinderpest in the Philippines and conceivably also could have been of some importance in other areas of Asia where swine commonly are kept in households. It was suggested [28] that the heads of affected cattle and yaks that were stored frozen on the roofs of houses might have harbored infection during the cattle plague epidemic that hit the northern areas of Pakistan in 1994. Apart from these possible exceptions, the most likely source of a fresh focus of disease is a newly arrived live animal. There is no carrier state in cattle capable of transmitting infection after recovery. The association of mild rinderpest with wildlife The combination of severe disease in wildlife and mild or inapparent infection in cattle has led some to believe that wildlife constitutes a reservoir of infection that transmits to cattle when they come into contact. Although the full dynamics of rinderpest behavior in wildlife have yet to be described, information generated over many years suggests that this situation is not the case and that the reservoir of infection is in cattle. Nevertheless, it is not uncommon for the virus to linger on for some time, particularly in large

528

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

populations of wildlife. For example, the large wildebeest herd of the Serengeti/Masai Mara ecologic system in Tanzania and Kenya maintained rinderpest virus for some time after it was eliminated from local cattle populations by repeated mass vaccination. Lacking opportunities for reinfection, it did die out within 3 years, however [29]. Clinical, serologic, and demographic studies conducted during the 1993 to 2001 epidemics in eastern Kenya argue against the lack of long-term, independent maintenance of rinderpest virus in wildlife [27; Richard Kock, MA, VetMB, Nairobi, Kenya, personal communication, April 2002]. Food and Agriculture Organization reports [23,24] from a rinderpest campaign conducted in southeast Asia in the 1950s and 1960s testify to the existence of a cattle-wildlife mild rinderpest axis in Cambodia, Laos, and Vietnam that is similar to that being described for Africa lineage 2 virus in the Somali ecosystem at present. In Vietnam, this axis might have persisted until as late as 1977 (official reports of Vietnam to OIE [30]). There is compelling evidence of the severity of rinderpest in wild animal populations in Africa, and it is undoubtedly a significant factor in their rapid decline in recent years [27]. Far from harboring rinderpest and threatening cattle, Africa’s wildlife heritage, already fragmented into relict populations by human settlement, is vulnerable to and highly threatened by the maintenance of rinderpest in the pastoralists’ herds of eastern Africa. The situation is critical. Recent events in East Africa have undermined confidence in the understanding that wild ungulates are unable to maintain rinderpest virus infection on their own without the opportunity for regular inputs of fresh infection from cattle. Some stakeholders are therefore pessimistic about the possibility of eradicating rinderpest from the Somali ecosystem. Nevertheless, experience from other campaigns illustrates that mild rinderpest, even if associated with wildlife as it was in West and Central Africa [30] and in southeast Asia [23,24], is still amenable to eradication through concerted action. Virulence A significant factor in the epidemiology of rinderpest is the variable virulence of different field strains of the virus. Given the existence of strains of varying virulence, it is clear that in nature, modulating selection pressures have produced both avirulent and highly virulent field strains. Practitioners are still far from understanding the nature of these pressures and how they work. Proof of their existence, at least in the laboratory, is shown by the propensity of virulent strains to attenuate when adapted to, and passaged in, unusual hosts (eg, rabbits, eggs, goats, and tissue culture). On the other hand, by needle-passaging in laboratory cattle, the virulence of a number of strains has been maintained at a constant level for a number of years. In the field, evidence of the workings of these pressures comes from two contrasting but consistent sets of observations. The first is that whenever

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

529

rinderpest gains entry into a totally naive population, its virulence increases. This occurrence is the general pattern at the start of an epidemic, and it seems that mutants of increasing virulence accumulate relatively quickly. Miniepidemics in the Gulf States in the early 1980s always yielded viruses that were highly pathogenic for cattle [13]. Whenever the virus becomes endemic within a given population, however, its virulence decreases, and remarkably mild strains have been isolated from both East Africa and Egypt [13,14]. From this finding, one can suggest that populations of susceptible cattle represent a selection pressure for virulence, and populations of partially immune cattle are a selection pressure for attenuation. The genetic constitution of the host also can influence the expression of rinderpest virulence; for example, Bos taurus cattle breeds are generally more susceptible to the ravages of the virus than Bos indicus and are possibly more likely to support the overgrowth of a more virulent strain. It therefore is perhaps not surprising that the most virulent strain known was isolated from a totally unvaccinated herd of Friesian and Holstein cattle in Saudi Arabia or that there seems to be an association between endemicity among Zebu cattle and the emergence of mild field strains. Virus strains differ markedly in the virulence with which they cause disease, and it is now clear that accompanying this variation are differences in the basic reproductive rates (R0) of the viruses [31], reflecting differences in transmissibility. Extending earlier modeling work [32] and using values of R0 derived from serologic data with other parameters characterizing the diseases caused by virulent and mild rinderpest viruses (as typified by African lineage 1 rinderpest virus in the Sudan and African lineage 2 rinderpest virus in Somalia), this approach is helping to clarify the means of virus persistence in populations of cattle through the use of stochastic state transition mathematical models [31]. Divergence of lineages and lessons regarding the control of rinderpest The Asian lineage Asia is probably where rinderpest first evolved, and the existence of a single Asian lineage suggests a long evolutionary passage free of radical pressure for genetic change. In recent times, representative isolates of the Asian lineage have been recovered from India, Iran, Iraq, Saudi Arabia, Kuwait, Oman, Pakistan, Sri Lanka, Turkey, and Yemen. The virulence of Asian lineage isolates tends to be high, sometimes to the point of peracuteness, and although there are indications that the virulence reduces in endemic situations, no genuinely subclinical strains of this lineage have ever been isolated. The virus that invaded Egypt in 1903 and that apparently came from Baghdad, however, was described as being characteristically mild in local Iraqi cattle. The existence of mild or even subclinical strains formerly was well recognized in the Near East. One report of the FAO Animal Production and Health Division for the Near East [33] went so far as to state

530

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

that ‘‘Transmission is primarily by means of direct contact transmission which is invariably introduced by live animals having had mild or subclinical infections’’ and ‘‘because of the intensive…vaccination campaigns and the circulation, and recognition, of mild strains of rinderpest virus, cases of rinderpest conforming to the classic descriptions…have, in recent years, become rarer making it difficult for spot diagnosis, based on clinical and post-mortem findings to be made.’’ Although there is no proof, it is tempting to suggest that the early viruses belonged to the Asian lineage, as did those viruses isolated in the 1980s. In mid-2002, because no outbreak associated with the Asian lineage was detected since the one that occurred in Pakistan in September 2000 [34], it is possible that this virus is close to extinction if not already eliminated. African lineage 1 and the twentieth-century introduction of rinderpest in Egypt Although there is a reasonably complete historical record of the entry of rinderpest into Africa and the devastation that it subsequently caused, this record cannot be matched with isolates that would allow one to observe the origins of the two African lineages that now exist. Practitioners, therefore, can only speculate as to what may have happened. One entry took place in 1903 in Egypt [35], with the introduction of a mild rinderpest strain from Mesopotamia (Iraq). The virulence of the virus obviously changed after it entered Egypt, and during 1903 and 1904, a major epidemic of rinderpest spread throughout the country in cattle and buffaloes. Interestingly, the veterinary authorities were aware of a risk of introducing rinderpest from this source. So much so that cattle from Asia Minor, probably from the Baghdad area, were screened specifically into an Alexandria slaughterhouse. This screening was carried out because it was recognized that rinderpest virus occurring in the Baghdad region in local, so-called ‘‘Baghdadli’’ cattle showed a low level of virulence; nevertheless, the virus entered. The significant point here is that once local transmission started (in naive Egyptian cattle and buffaloes), the virus apparently gained significantly in virulence. Subsequently, rinderpest became endemic in Egypt, causing severe losses every 10 to 20 years until as late as 1963 (Table 1). Significantly, in 1953 it was noted that the disease did not always appear in its acute form and that mild cases were occurring. Because Egyptian history does not record any further external rinderpest introduction, it seems possible that the virus causing all of these epidemics was descended directly from the 1903 strain. In 1982, after an absence of nearly 20 years, rinderpest reappeared, causing clinical cases in feedlot cattle. The epidemic was severe and lasted for 5 years, ending in 1986. A virus was isolated from Fayoum in 1984 and subsequently was characterized as Africa lineage 1. From this finding, it can be argued that exposing rinderpest virus to an entirely new population on a new continent creates a selection pressure for the emergence of a new lineage.

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

531

Table 1 Severity of rinderpest epidemics in Egypt, 1903–1986 Years

Rinderpest deaths in bovines

1903–1904 1917 1921–1923 1945–1947 1950–1953 1961–1963 1982–1986

354,647 500 697 831 800 315 11,423

From Mostaffa OR. Country report to the Ninth Annual OAU-IBAR-PARC East African Coordination Meeting. Machakos. (Kenya): 1999; with permission.

In recent times, lineage 1 strains have been recovered from southern Sudan, western Kenya, Ethiopia, and eastern Nigeria in 1983, coinciding with pandemic recrudescence of rinderpest across sub-Saharan Africa in the early 1980s. From this evidence, it is possible to suggest that lineage 1 may have spread south from Egypt to become endemic in southern Sudan, Uganda, and Ethiopia, from where, when trade in live cattle became profitable, it could have spread to Kenya or across central Africa to Nigeria. The other significant point to emerge from these studies is that the Egypt 1984 isolate was of unusually low virulence in experimental cattle and that, by implication, it had survived by undetected transmission in village cattle from 1963 to 1982. Yet when it gained entry to a feedlot where cattle were probably more highly stressed than cattle in surrounding villages, it regained and maintained a higher level of virulence. African lineage 2 and the nineteenth-century introduction of rinderpest to East Africa Under totally unrelated circumstances, rinderpest became widely established in East Africa as the result of introduction into eastern Africa, notably Eritrea, in approximately 1895. Because the virus probably came from India it can be noted that, as with the Egyptian introduction, it probably belonged to the Asian lineage. As this virus spread southward and westward, its impact reached pandemic proportions in the totally susceptible populations of domestic cattle and wildlife species it encountered. It subsequently became endemic across West, central, and eastern Africa but was totally eliminated from the southern part of the continent by 1905. No early East or West Africa strains exist, but since the 1950s, strains of rinderpest isolated on both sides of the continent have belonged to a second lineage, African lineage 2. Because the distribution of these lineage 2 representatives roughly coincides with that of the spread resulting from the nineteenth-century introduction, it is proposed that they should be viewed as the successors to this virus. Valid or not, it can nevertheless be suggested that, as with lineage 1, exposure to a totally

532

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

susceptible population acted as a selection pressure resulting in the emergence of a second new African lineage. Although lineage 2 originally may have swept across the whole of subSaharan Africa, it seems to have been displaced subsequently from central Africa by the southward extension of lineage 1. This occurrence resulted in the creation of two separate zones of endemic lineage 2 infection, one in East Africa and one in West Africa. By the 1960s, a seemingly highly modified, mild variant of lineage 2 had evolved in East Africa. The significance of this virus was, and still is, that it seemed to die out, yet it continued to transmit within the region’s cattle population. Having apparently been eradicated in the early 1960s, this virus re-emerged in Kenya in 1994 [36]. As with lineage 1 virus, lineage 2 virus has shown an ability to persist undetected for long periods within reasonably well-monitored livestock populations. In 1994 to 1996 and again in 2001, the East African lineage 2 virus demonstrated a considerable virulence for wild African buffaloes. It may be supposed, then, that if it gained access to a highly susceptible cattle population, it would quickly regain cattle virulence. In this context, it has now become clear that this virus is an exceedingly dangerous one, and it may spoil Africa’s future as a rinderpest-free continent. The effect of epidemiologic understanding on the handling of control and eradication campaigns To a large extent, rinderpest eradication has proceeded on the basis that strains are so closely related that the currently recognized vaccine is equally efficacious against all of them and that, as an understanding of the existence of lineages emerged, this dogma was not going to be challenged seriously. Yet problems remain for which an understanding of the epidemiology of the virus is crucial. In East Africa, the rediscovery of lineage 2 virus after a gap of 30 years showed how little practitioners appreciated the possibility that this situation could happen and how seriously consequences must be considered. It must be questioned whether the continuous use of vaccine to immunize only part of a population may have contributed to the reduction of field virulence to the point of crypticism. If one thinks the answer to this question is yes, one must do everything possible to eradicate lineage 2 with a minimum application of vaccine. But one also must question what will happen if a country that thinks it has eradicated lineage 2 virus still is infected with it and then stops vaccinating. Clearly, the mild virus must be eliminated, but it is only likely to happen within a carefully managed program. Differential diagnosis It is clear that the variability in clinical appearance of rinderpest requires that surveillance for rinderpest must be focused on detecting a

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

533

‘‘stomatitis-enteritis syndrome.’’ Animals meet the case definition if they exhibit bilateral ocular and nasal discharges combined with one or more symptoms such as fever, oral erosions, salivation, diarrhea, corneal opacity, or death. Corneal opacity is not a usual sign of rinderpest in cattle and buffaloes, but it has been observed together with other ocular lesions in wildlife [27], and it is retained because its inclusion does not expand the caseload greatly. The main causes of the stomatitis-enteritis syndrome are considered in the following paragraphs. Bovine virus diarrhea and mucosal disease Both cattle disease complexes, bovine viral diarrhea (BVD) and mucosal disease (MD), are manifestations of infection with a single bovine pestivirus. Infection is ubiquitous, with approximately 50% to 75% of cattle showing serologic evidence of infection. Merely demonstrating antibody to BVD virus in an animal affected by a rinderpest-like disease does not confirm a causal link; failure to appreciate this fact frequently has compromised rinderpest investigations. BVD virus infection can occur at any time of life and is usually subclinical or causes a transient, mild disease; severe disease is rarely seen and is usually complicated by intercurrent infection. The essence of the difference between BVD and MD is that MD occurs only as a late sequel to intrauterine infection of the fetus up to 125 days of gestation and an induced life-long, persistent infection [37]. Despite being epidemiologically distinct, it is acute MD that most commonly may be confused with rinderpest. As with rinderpest, cattle with MD are depressed and anorexic; they have leukopenia with a high fever and may show epiphora, ptyalism, and profuse diarrhea, even dysentery. Erosions that become ulcerated commonly are found in the oral cavity and extend into the esophagus. At necropsy, lesions are seen to extend throughout the intestinal tract and involve necrosis of intestinal lymphoid tissue. Mortality approximates 100% and occurs within a week of the appearance of signs. Although MD is, strictly speaking, not contagious, several cases can occur in a herd within a short space of time (in animals of a similar age because of the clustering of the vulnerable persistently infected animals), giving an appearance of spread. Infection only rarely seems to spread to neighboring farms and herds, however. A chronic form of BVD also has been described in persistently infected cattle. These animals lose condition progressively, have intermittent diarrhea, and are often lame owing to ulceration of interdigital skin and coronary bands. Acute postnatal BVD infection is generally mild, even if followed by abortions and stillbirths in pregnant cows, yet clinically severe disease also is seen. Severe disease might take on a hemorrhagic appearance, in particular with petechial hemorrhages and ecchymoses in the mouth, on the sclera and conjunctiva, and in lymph nodes. Dysentery may be present. In this form of the disease, morbidity is high and mortality is variable, sometimes high. All ages of cattle may be affected, and the disease can spread

534

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

from herd to herd. One genotype of BVD virus (type 2) is responsible for this severe hemorrhagic disease [38]. Clearly, the different forms of BVD and MD should raise suspicions of classic rinderpest and infection with mild rinderpest virus strains. Such similarities should initiate diagnostic investigations for rinderpest, even in countries considered at low risk for introduction, if the national disease surveillance (‘‘early warning’’) system is functioning adequately. Malignant catarrhal fever Malignant catarrhal fever (MCF) also resembles rinderpest, except that it is not contagious among cattle. It is an acute disease with clinical signs bearing sufficient resemblance to rinderpest to warrant its inclusion in differential diagnosis. MCF is caused by a Herpesvirus that in parts of Africa is maintained as a silent infection in wildebeest (Connochaetes sp). Wildebeest calves excrete virus, contaminating pasture and water for a short period after birth. Cattle grazing the contaminated pastures or drinking water in this limited period go on to develop MCF. The occurrence of wildebeestassociated MCF is therefore highly seasonal, and a history of possible contact between cattle and calving wildebeest is relevant diagnostically. In other parts of Africa and throughout the world, a closely related virus is harbored by sheep, and infection of cattle occurs at the time of lambing. Morbidity is low, but the case-fatality rate is high. Clinically, the ‘‘headand-eye’’ form of MCF is characterized by pyrexia, anorexia, and marked depression, with a course of 1 to 2 weeks before death. During this period, a bilateral nasal discharge develops, serous at first but quickly becoming mucoid and then mucopurulent. Late in the disease, the nostrils become encrusted and completely blocked by discharge. In the eye, serous discharge becomes mucopurulent and, unlike rinderpest, this discharge accompanies a highly characteristic, centripetal corneal opacity. Opacity progresses to complete blindness, is usually bilateral, and is associated with photophobia. In the mouth, there is diffuse superficial necrosis of the gums, cheeks, cheek papillae, tongue, and hard palate. A more acute form of MCF occurs in which eye lesions do not develop. At necropsy, the abomasal mucosa is hyperemic and zebra stripes may be seen in the large intestine. Superficial lymph nodes are greatly enlarged, and edematous and foci of lymphocytic infiltration may be visible on the cut surface of the kidney. Infectious bovine rhinotracheitis Infectious bovine rhinotracheitis (IBR) is caused by a herpesvirus, bovid herpesvirus 1 (BHV-1), of which cattle are the principal host. The virus is distributed widely, and carrier cattle maintain the virus for long periods through latency established in the neurones of ganglia. Originally, a genital virus associated with infectious pustular vulvovaginitis, evolution to respiratory

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

535

infection is believed to have occurred in feedlots. The respiratory disease is severe in intensive husbandry conditions, such as feedlots, and rare in range conditions. Epidemics of IBR in feedlots may have a morbidity rate approaching 100% but a case-fatality rate generally less than 5%. Clinical IBR is characterized by fever, tachypnea, reduced appetite, cough, serous to mucopurulent ocular and nasal discharges, and weight loss. In severe cases, necrosis of the nasal mucosa can occur that may extend to hyperemia and necrosis of the muzzle (so-called ‘‘red nose’’). Animals may be reluctant to swallow and may drool saliva. Particularly in young calves, diarrhea can be a result of systemic infection with BHV-1 and is often fatal. Ulceration of the mucosa of the mouth, esophagus, and forestomach has been described. Confusion between rinderpest and IBR is clearly possible. Foot-and-mouth disease Like rinderpest, foot-and-mouth disease causes fever and lesions in the mouth, but these lesions are primarily vesicular. Although early unruptured or freshly ruptured vesicles in the mouth are differentiated easily from the erosions that typify rinderpest, older, severe lesions with extensive fibrin coating and secondary bacterial infection sometimes can cause confusion. Rinderpest does not cause lameness, which is a consistent feature of footand-mouth disease. Peste des petits ruminants To a considerable extent, the recent clinical and laboratory diagnosis of rinderpest is compounded by the existence of a second cross-related morbillivirus disease of domestic animals, peste des petits ruminants (PPR). There is little doubt that rinderpest occasionally has caused disease in sheep and goats, primarily in Asia, yet there undoubtedly has been much confusion between rinderpest and PPR in these species. PPR virus causes a severe disease in sheep and goats that bears a striking resemblance to rinderpest. The signs in typical cases include a necrotic stomatitis and nasal and ocular (to the extent that the eyelids mat together) discharges and diarrhea, accompanied by fever, anorexia, depression, and high mortality rates. Coughing and sneezing are common, with bronchopneumonia a marked feature of the pathology. The literature tends to the incorrect conclusion that PPR is a more severe disease of goats than sheep, but in fact it can be equally pathogenic for either species. It seems that goats tend to be affected more frequently in Africa and sheep in Asia, however. It follows that sheep or goats with oculonasal discharges and oral necrosis should arouse suspicion of either rinderpest or PPR, and laboratory assistance should be sought. PPR does not cause disease in cattle [39] but may well do so in domestic buffaloes [18]. Accordingly, buffalo cases involving necrotic stomatitis should arouse suspicion of either disease, and again, laboratory assistance should be sought.

536

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

Laboratory confirmation of rinderpest and differentiation from peste des petits ruminants Unequivocal confirmation of a provisional diagnosis of rinderpest is provided by isolation of rinderpest virus or the detection of rinderpest-specific viral RNA together with their further characterization. Isolation of virus is preferable, for it provides a virus that can be used for biologic transmission and characterization studies and archived for future use. Details of the standard methods used in the laboratory diagnosis of rinderpest may be found in the fourth edition of the Office International des Epizooties’ (OIE) Manual of Standards for Diagnostic Tests and Vaccines [40]. The tests described in it reflect the evolution of diagnostic tests for rinderpest, starting with a group-specific test developed before the need to differentiate PPR and rinderpest was appreciated and ending with an ability to differentiate rinderpest-specific gene sequences in material from infected animals. Nevertheless, owing to the importance of assessing the phylogenetic character and virulence of the virus, it must be emphasized that no diagnosis is complete unless the virus also is isolated. The agar-gel immunodiffusion test Virus-specific antigens are produced in the cells of affected hosts, and their presence can be determined in an extremely basic agar-gel immunodiffusion test. The test may be conducted in Petri dishes or on glass microscope slides using a 1% aqueous solution of any high-quality agar or agarose. The closer the wells are placed, the shorter the reaction time will be; using slides, 3-mm diameter wells at 2 mm periphery to periphery and a potent rabbit hyperimmune rinderpest antiserum, the test can be read in a little more than 1 hour and therefore serves as a rapid diagnostic test. It generally is used to demonstrate the presence of precipitinogens in the ocular secretions of infected animals. These samples should be collected during either the prodromal or erosive phases using cotton wool buds maneuvered beneath the upper and lower eyelids. Only in cattle does a positive test result imply a specific rinderpest diagnosis; in buffaloes and in sheep and goats, a positive test result indicates that either rinderpest or PPR is involved. The immunocapture ELISA test An immunocapture ELISA test has been devised [41] and is available as a commercial kit. In addition to being able to provide a confirmatory diagnosis of rinderpest, it also distinguishes between rinderpest and PPR virus. It follows that in countries where both diseases occur, this test should be used in the differential diagnosis of rinderpest-like outbreaks in sheep or goats. The test uses monoclonal antibodies (MAbs) directed against the N protein of the two viruses. One MAb, with a reactivity against both viruses, is used as a capture antibody, whereas a second biotinylated MAb specific for a

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

537

nonoverlapping antigenic N protein site and specific against either rinderpest or PPR is used to determine which N protein has been captured. The reverse-transcription polymerase chain reaction A reverse-transcription polymerase chain reaction (RT-PCR) method for the differential diagnosis of rinderpest and PPR has been described [42]. The cDNA synthesis is carried out using random hexanucleotide primers to enable several different specific primer sets to be used in the PCR amplification step. Aliquots of the resulting cDNA are amplified using at least three primer sets that can detect and differentiate between the two morbilliviruses. These primer sets include two ‘‘universal’’ sets based on highly conserved regions in the phosphoprotein and nucleoprotein genes that should detect all morbilliviruses and rinderpest virus–specific and PPR virus–specific sets based on sequences in the fusion protein genes of each virus. The PCR products are analyzed on a 1.5% agarose gel. Positive reactions should be confirmed either by using ‘‘nested’’ primer sets based on the F gene sequences or by sequence analysis of the DNA product. It is important to use more than one set of primers for the PCR step when testing for the presence of RNA viruses, because their nucleotide sequences can vary significantly, and one change at the 3¢-end of the primer sequence may result in failure of the primers to amplify the DNA. Pen-side diagnosis of rinderpest A rapid chromatographic strip test for the pen-side diagnosis of rinderpest virus has been described [43]. In a series of recent trials, its principal value was found to be that of instilling confidence among field officers that their clinical appraisal was correct in cases that were bordering on subacute [34]. Virus isolation Rinderpest virus can be cultured from the leukocyte fraction of whole blood that has been collected into heparin or ethylenediaminetetra-acetic acid anticoagulants at final concentrations of 10 IU per mL and 0.5 mg per mL, respectively. Samples should be thoroughly mixed and transferred to the laboratory on ice but not frozen. Virus also can be isolated in samples obtained from the spleen or the prescapular or mesenteric lymph nodes of dead animals; these samples may be chilled to subzero temperatures. Samples are suspended in cell-culture maintenance medium and distributed onto established roller-tube monolayers of B95a Marmoset lymphoblastoid cells, primary calf kidney cells or African green monkey kidney (Vero) cells. The monolayers should be re-fed periodically and observed microscopically for the development of cytopathic effects characterized by refractility, cell rounding, cell retraction with elongated cytoplasmic bridges (stellate cells), or syncytial formation.

538

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

Serologic tests A competitive ELISA test (c-ELISA) is available for the detection of rinderpest antibodies in the serum of animals of any species previously exposed to the virus [44]. This test is prescribed by the OIE for international trade. It is based on the ability of positive test sera to compete with a rinderpest antiH protein MAb for binding to rinderpest antigen. The presence of such antibodies in the test sample blocks binding of the MAb, producing a reduction in the expected color reaction after the addition of enzyme-labeled antimouse IgG conjugate and a substrate or chromogen solution. This test can be used in epidemiologic investigations to determine the distribution of the virus based on the presence of recovered animals in unvaccinated populations or, alternatively, it may be used to determine the effectiveness of recent vaccination campaigns. The virus neutralization test, whether performed in rolled-tube cultures or microtiter, remains the gold standard test; if it were easier and cheaper to perform, it would be the method of choice. Improving the tools available for diagnosis and serosurveillance The H MAb c-ELISA was developed for the seromonitoring of vaccination programs using the tissue culture–attenuated rinderpest vaccine, which it did well. As global rinderpest eradication is moving rapidly away from vaccination to the verification of freedom from rinderpest, the emphasis is now on the use of serologic tests to detect evidence of field virus circulation and for retrospective diagnosis of suspicious disease events. It seems that the c-ELISA might lack sensitivity, which is creating problems, particularly in the diagnostic context. It seems that the test does not become positive for a considerable time after infection, even if it performs well in terms of specificity. The performance characteristics are being evaluated at present, together with those of a number of other candidate assays based on synthetic peptides or expressed recombinant antigens.

Control Ever since the development of State Veterinary Services began, there has been a consensus among them that limiting the ravages caused by rinderpest was a priority issue and an essential prerequisite to the development of modern livestock industries. It was demonstrated quickly that rinderpest control could be succeeded rapidly—there being no technical barriers— byrinderpest eradication. Contrarily, stopping short of eradication required an annual reinvestment in expensive control measures. The Russian experience of the early twentieth century showed that draconian zoosanitary measures were all that was required to achieve eradication. The search for less bureaucratic methods, however, produced live attenuated vaccines, and as was shown in China, another road to eradication was opened.

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

539

Effective as vaccination could be, its pursuit had to be intensive enough to halt transmission completely throughout the whole of an infected area while the possibility of re-infection from an external source had to limited. This last point had particular relevance for countries that have long international borders that are open to the ingress of livestock from their neighbors. In Africa this has been, and still is, an ongoing obstacle to both control and eradication. The African experience also showed that when neighbors involved themselves in coordinated control programs, rapid eradication was perfectly achievable. The fact that rinderpest still exists in one region of Africa is a reminder of the need to re-examine the basic lessons of control leading to eradication. In India it was possible to see that vaccine was viewed as an effective means of controlling rinderpest but apparently was failing in achieving eradication. Whereas China eradicated rinderpest between 1950 and 1955, in India eradication took another 40 years to achieve. During this period, it was possible to see vaccine as a factor controlling the virus to the extent that a vibrant dairy industry could develop, failing in that vaccination campaigns never reached the level of intensity required to break the virus’ transmission chain in all parts of the country. In many ways, it was by redefining the criteria relating to the use of vaccine that India and Ethiopia finally succeeded in eradicating rinderpest in 1995. Because vaccine will still play a major role in the eradication of rinderpest in Africa, strategy issues relating to its use are discussed in the following section.

Aspects of rinderpest control and eradication Vaccination In endemically infected countries, veterinary administrations generally have chosen to reduce the incidence of disease outbreaks to ‘‘manageable’’ proportions through the mass application of prophylactic vaccine with the option of using zoosanitary measures for the later stages of their control program. Essentially, the prophylactic approach sets about turning susceptible hosts into immune hosts on such a large scale that new infections cannot occur. Theoretically adopting this policy can bring about rapid success but requires the authorities to render all susceptible animals immune at much the same time, a process that continually proves difficult to achieve and is preceded by a need to know the whereabouts of the virus. Mass vaccination requires investment capital for the development of vaccinemanufacturing facilities, cold chains, campaign mobility, and campaign manpower. If well managed, however, quick results are possible in the form of a total reduction in the incidence of outbreaks and the ability to test whether or not eradication has been achieved. The history of vaccination campaigns, however, shows that they often become institutionalized at low uptake levels, a circumstance that can render residual foci of infection harder

540

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

to find than ever. The casual application of vaccination therefore can conserve rinderpest rather than eliminate it. Rinderpest vaccine should be used only when there is a well-defined problem to solve and a short-term plan for doing so.

Zoosanitary control In the case of infection outside areas of known endemicity, biosecurity considerations automatically would dictate the implementation of a stamping-out policy involving the destruction of all stock on the infected premises and on any dangerous contact premises. Rinderpest, however, although greatly feared because of its association with high fatality rates, is not infectious over long distances. In endemic areas where the destruction of affected animals is often extremely unpopular and where the threat of destruction often leads to the illegal movement of infected animals, improved control can come from a policy of treatment and on-farm quarantining. Supplementary measures must include the prohibition of all off-farm animal movement of livestock unless for slaughter and products (eg, untreated milk), movement restrictions in the surrounding area (including the closure of neighboring livestock markets), and livestock surveillance activities within a radius of several miles of the infected premises. Of course, such biosecurity measures clearly require legislative backing and the necessary political will to invoke them, and they always will be unpopular at a local level, although less so if water and fodder are provided. In Pakistan, for example, no outbreak of rinderpest has been reported since September of 2000. In the event of a further outbreak, the current control policy calls for the implementation of zoosanitary controls in the affected village and ring vaccination of all cattle and buffaloes in surrounding villages.

National programs for eradication The secret behind India’s and Ethiopia’s success (two notable achievements in areas of long-standing endemicity) in eradicating rinderpest between 1992 and 1995 lies in reconceptualizing their programs within a time-bound framework. It now can be said that this example is a lesson to be applied in all areas where there are good prospects of eliminating endemic rinderpest through focused vaccination campaigns within an epidemiology-based program. Before the initiation of any campaign, the following criteria need to be fulfilled: • • • • •

Adequate tools A sound strategy International cooperation Sufficient finance Sound program management

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

541

Tools A live attenuated rinderpest vaccine with an OIE product approval exists. For use in the field, vaccine is distributed as a freeze-dried product with a considerable shelf life within an elementary cold chain. With postrehydration degradation constants of 0.016 and 0.043 at 4C and 37C, respectively, reconstituted vaccine can be held at 4C for 31 hours or at 37C for 11 hours, and at the end of these periods, the vaccine still should conform to international norms with respect to field-dose levels. A product of enhanced thermostability is also available [45] and has had a major impact in facilitating rinderpest eradication programs in remote areas using community-based animal health worker programs [46]. Assurance of vaccine quality proved to be of crucial importance in improving the efficacy of vaccination campaigns under PARC. Not only did the work of the Pan-African Veterinary Vaccine Centre provide guidelines for vaccine production and quality assurance but by providing an independent testing service, it helped to exclude poor vaccines from use. The standards of vaccine production improved progressively, with virus titer rising and the pass rate increasing from 47% to 94% between 1994 and 1998 (J. Litamoi, BVM, MSc, Debre Zeit, Ethiopia, personal communication, September 1999). The only limitation imposed by these vaccines is that it is impossible to distinguish between infection with wild virus and vaccine virus, so it becomes difficult to define an infected area if part of it is being casually vaccinated. In an attempt to overcome this problem, marked vaccines [47] and vaccinia-recombinant vaccines [48] are advancing in development. Strategy Contemporary strategies should be based on a prior understanding of the boundaries of the infected area and an understanding of the epidemiology of the virus within that area, including the lineage of the virus and the transmission chains responsible for maintenance and spread. There also must be prior understanding of the current virulence profile of the endemic virus in each of the species affected. Assuming domestic cattle to be the most important species, a program then should be established that would allow for almost universal vaccination of all cattle in the infected area; in practice, this task is achieved best by at least two rounds of back-to-back vaccination. The success of the campaign then would be evaluated by seromonitoring, clinical surveillance, and serosurveillance among unvaccinated yearling or older animals. Thereafter, further defined foci would be treated by ring vaccination combined with zoosanitary controls. International cooperation National eradication campaigns can commence at any time and can be completely successful, but if the virus persists in neighboring countries, there will be a constant danger of the reintroduction of infection and the loss of all

542

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

that has been achieved. Although vaccination belts have been considered as a means of ensuring that reinfection does not take place, their effectiveness is questionable, and they represent an unwelcome expense to a country that has already achieved eradication. It is therefore important that where residual pockets of infection occur in more than one country, control and eradication are progressed within a regional context, with each infected country committing itself to rinderpest eradication at more or less the same time. External funding will be required for some countries to participate and to manage the coordination. Financing eradication Countries that still are affected by rinderpest, even if only by virtue of neighboring with countries harboring infection, inevitably subscribe to ongoing national control programs. Relative to the cost of direct disease losses, the costs of such vaccination campaigns are extremely high. The conclusion to be drawn is that, even if expensive in the short term, eradication is the only solution that can be advocated. Before realigning an existing control program as an eradication program, however, it is important to examine the financial implications of this transition. In so doing, it is essential to realize that eradication programs must be committed totally to obtaining a rapid and absolute result and that there will be an escalation of short-term expenditures, with, of course, the expectation of massive savings in the years to come. It is up to participating countries to determine whether, in moving toward eradication, they need to make fresh investments to improve their vaccine manufacture, cold chain, vehicles, vaccination equipment, serosurveillance, and disease reporting. If external financial assistance is needed by way of loans or grants, solving this issue must be part of the project planning activity. It should be central to these financial considerations that rinderpest eradication be regarded as a public ‘‘good’’ and that appropriate public funding be made available. Program management At national and international levels, rinderpest program management is important, and specific management may need to be created. The national program manager must have a strong working relationship with the district staff actually implementing the program. The manager should be aware of the international context within which the national program is to become operative and should develop an appropriate annual strategy, either for the country as a whole or in zones within the country. The project manager also should have responsibility for initiating and supervising any research necessary for furthering the national program and should have continuous access to the resources of a reference laboratory. As is the case with all programs aimed at the progressive control of transboundary animal diseases, there is little chance of effective action unless a strong line-managed veterinary service with an unbroken line of command

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

543

and information flow in both directions between the chief veterinary officer and field workers exists. International organizations such as FAO and OIE have an important but indirect management role to play in any national program; the FAO through the provision of expert advice and assistance and the OIE through the OIE Pathway. The latter already influences in a number of countries program managers who act in the knowledge that this method is the only route by which their results will receive full international credit.

International recognition of rinderpest eradication Rinderpest eradication will not be complete until sufficient assurance of the fact has been generated. In reality, this task requires a process of international accreditation. The OIE bears responsibility for providing guidelines to member countries in regulatory matters pertaining to disease control. Working with its partners, it established the OIE Pathway [49], which together with its International Animal Health Code chapter on rinderpest [50], is intended to act as a framework for countries to guide national rinderpest eradication programs. The OIE Pathway stipulates conditions for a three-step progression through a self-declared ‘‘provisional freedom from disease’’ to internationally recognized ‘‘freedom from disease’’ to internationally recognized ‘‘freedom from infection.’’ The entire process takes 6 or 7 years from the last recognized case of disease and requires a national authority able to make submissions to the OIE. Although this process functions well for many countries stimulated by the advantages to be gained in livestock trading, for others in which livestock trade is immaterial, it offers little incentive. For Somalia, probably the last and most difficult of rinderpest reservoirs to be addressed, lack of a unified government precludes progress in this context. FAO is working with OIE to explore supplementary procedures for assured verification of rinderpest freedom.

Prospects for achieving global eradication An FAO Expert Consultation meeting held in Rome in 1992 [51] reaffirmed the general consensus of belief that the total global eradication of rinderpest was desirable, achievable, and even feasible. The GREP was founded based on this belief, and 10 years later, there is no reason to change this basic tenet even if the process has turned out to be rather different from what was envisaged. The original concept was that internationally funded distinct regional campaigns would take on the work of eradication under a coordination umbrella provided by FAO. In reality, only the PARC, already in place at the time, continued to function and has now been replaced by the Pan-African Programme for the Control of Epizootics, both programs being long-term ones funded by the European Union. The West

544

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

Asian Rinderpest Eradication Campaign functioned from 1989 to 1994 and the South Asian Rinderpest Eradication Campaign was never initiated. The coordination role outside Africa has been undertaken by FAO since 1994, when there was an intensification of attention to GREP with the founding of FAO’s Emergency Prevention System for Animal and Plant Pests and Diseases. By 1996, it was possible to speak authoritatively of the real distribution of rinderpest in the world: at that time, persisting infection combined with sporadic reintroductions and recrudescence in South Asia; the Arabian peninsula; the Kurdish triangle of Turkey, Iran, and Iraq; inter-related pastoral ecosystems of Sudan, Kenya, Uganda, and Ethiopia; the Somali pastoral ecosystem; and some suspicion about China, Russia, Mongolia, and the Central Asian Republics. Since then, virtually all of the uncertainties have been resolved, and real progress has been made in eliminating reservoirs of infection. In 2002, there is growing confidence that only one reservoir of infection is present. The Indus River buffalo tract is currently the focus of intensive surveillance activities with assistance from the European Union, despite which no virus activity has been detected for more than 1 year. The Somali focus is the greatest cause for concern because the country represents a continuing complex emergency, and rinderpest eradication efforts lag behind those in the other arenas. Frustratingly, a lack of security and effective infrastructure also is combined with the difficulty posed by the mild nature of the virus currently present, making surveillance and focusing of control problematic. Even in the case of the Somali focus, however, there is some cause for optimism. Under the auspices of the European Union– funded Pan-African Programme for the Control of Epizootics and its United Kingdom–funded Community Animal Health and Participatory Epidemiology project, significant progress has been made in the past 2 years in defining the extent of rinderpest infection in Kenya and Somalia. The year 2002 should prove a milestone in initiating action that will eliminate this last reservoir of persisting rinderpest. As described previously, the pastoral communities east of the Nile in southern Sudan certainly were infected until recently, but as the subject of intensive eradication effort, there is growing confidence that eradication has been achieved. The challenge is to complete the eradication of the remaining reservoirs within the next 2 years and to build up surveillance through directed surveys to provide adequate confirmation of rinderpest absence everywhere. The precise mechanism for this goal needs to be worked out, and the process has started. It is becoming increasingly clear that the process would be aided greatly by establishment of regional coordination units to continually stimulate progress, to provide technical guidance, and to act as the secretariat for regional GREP committees to coordinate submissions for recognition of disease freedom. The international community must decide if it wishes to seize the opportunity presented for the first time ever to consign to history a major plague

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

545

of livestock and to safeguard the livelihoods and nutrition of those families dependent on livestock. The alternative of failing once again to carry the process through to full eradication would be shameful, and the prospect of resulting massive pandemics that would result, followed by a return to widespread endemicity with periodic epidemics and occasional pandemics, is horrendous to contemplate. The fact that rinderpest has not featured in any of the emergency situations in the world in the past few years is in sharp contrast to earlier times and is testimony to the great advances that have been made in reducing the global weight of infection. Yet that favorable situation itself risks generating the very complacency that has caused previous eradication efforts to fail. Unfortunately, success breeds complacency. The means of eradicating rinderpest are known and the tools are at hand; only time will tell if efforts will be sustained to achieve a world without rinderpest by 2010.

References [1] Scott GR, Provost A. Global eradication of rinderpest. Background paper prepared for the FAO Expert Consultation on the Strategy for Global Rinderpest Eradication, Rome, October 1992, 109 pp. [2] Barrett T. Morbilliviruses: dangers old and new. In: Smith GL, Irving WL, McCauly JW, Rowlands DJ, editors. New challenges to health: the threat of virus infection, SGM symposium 60. Cambridge (UK): Editors Cambridge University Press; 2001. p. 155–74. [3] Vizoso AD, Thomas WE. Paramyxovirus of the Morbilli group in the wild hedgehog Erinaceus europaeus. Br J Exp Pathol 1981;62:79–86. [4] Coulter GR, Storz J. Identification of a cell-associated morbillivirus from cattle affected with malignant catarrhal fever: antigenic differentiation and cytologic characterisation. Am J Vet Res 1979;40:1671–7. [5] Norrby E, Sheshberadaran H, McCullough KC, et al. Is rinderpest virus the archevirus of the morbillivirus genus? Intervirology 1985;23:228–32. [6] Diamond J. Guns, germs and steel. London: Chatto and Windus; 1997. p. 206–7. [7] Wamwayi HM. Efficacy of some chemicals and disinfectants against rinderpest virus. Bulletin of Animal Health and Production in Africa 1989;37:255–60. [8] Chamberlain RW, Wamwayi HM, Hockley E, et al. Evidence for different lineages of rinderpest virus reflecting their geographic isolation. J Gen Virol 1993;74: 2775–80. [9] Rossiter PB. Rinderpest. In: Coetzer JAW, Thomson GR, Tustin RC, editors. Infectious diseases of livestock with special reference to Southern Africa. New York: Oxford University Press; 1994. p. 735–57 [chapter 74]. [10] Curasson G. La peste bovine. Paris: Vigot; 1932. [11] Liess B, Plowright W. Studies on the pathogenesis of rinderpest in experimental cattle. I. Correlation of clinical signs, viraemia and virus excretion by various routes. Journal of Hygiene 1964;62:81–100. [12] Wafula JS, Rossiter PB, Wamwayi HM, et al. Preliminary observations on rinderpest in pregnant cattle. Vet Rec 1989;124:485–6. [13] Taylor WP. Epidemiology and control of rinderpest. Scientific and Technical Review of the Office International des Epizooties 1986;18:407–10. [14] Plowright W. Some properties of strains of rinderpest virus recently isolated in East Africa. Res Vet Sci 1963;4:96–108.

546

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

[15] Wamwayi HM, Kariuki DP, Wafula JS, et al. Observations on rinderpest in Kenya, 1986–1989. Scientific and Technical Review of the Office International des Epizooties 1992;11:769–84. [16] Bansal RP, Joshi RC, Kumar S. Occurrence of rinderpest in pigs in India. Bull Off Int Epizoot 1974;81:305–12. [17] Govindrajan R, Muralimanohar B, Koteeswaran A, et al. Occurrence of rinderpest in European pigs in India. Vet Rec 1996;139:473. [18] Taylor WP, Diallo A, Gopalakrishna S, et al. Peste des petits ruminants has been widely present in southern India since, if not before, the late 1980s. Prev Vet Med 2002;52:305–12. [19] Taylor WP. The susceptibility of the one-humped camel (Camelus dromedarius) to infection with rinderpest virus. Bull Epizoot Dis Afr 1968;16:405–10. [20] Singh KV, Ata F. Experimental rinderpest in camels. Bull Epizoot Dis Afr 1967;15:19–23. [21] Babu MM, Gopal T, Ananth M, Gopal Rao BS, et al. Rinderpest in a bison Bos gaurus. Indian Journal of Veterinary Pathology 1990;14:75–6. [22] Singh VP, Murty DK. An outbreak of rinderpest in wild spotted deer (Axis axis). Indian Vet J 1979;56:988–90. [23] Food and Agriculture Organization. Lutte contre les maladies animales. Rapport aux gouvernements de la Birmanie, du Cambodge, du Laos, de la Thailande et du Viet-nam by ´ largi d’Assistance Technique, Rapport no. 1202, Rome, Dr. J. Hudson. FAO Programme E Italy, 1960. [24] Food and Agriculture Organization. La campagne de lutte contre la peste bovine. Rapport au gouvernement du Cambodge by Dr. H.L. Stoddard. FAO Programme Elargi d’Assistance Technique, Rapport no. 1749. Rome: FAO; 1964. [25] Kurchenko FP. Prophylaxis and measures to eliminate rinderpest. Veterinary Science 1995;8:27–31. [26] Scott GR. Rinderpest. In: Davis JW, editor. Infectious diseases of wild mammals. 2nd edition. Ames: The Iowa State University Press; 1981. p. 23–30. [27] Kock RA, Wambua JM, Mwanzia J, et al. Rinderpest epidemic in wild ruminants in Kenya 1993–97. Vet Rec 1999;145:275–83. [28] Rossiter PB, Hussain M, Raja RH, et al. Cattle plague in Shangri La: observations on a severe outbreak of rinderpest in northern Pakistan 1994–1995. Vet Rec 1998;143:39–42. [29] Plowright W, McCulloch B. Investigations on the incidence of rinderpest virus infection in game animals of Northern Tanzania and S. Kenya 1960/63. Journal of Hygiene 1967; 65:343–58. [30] Food and Agriculture Organization. Rinderpest in wildlife in sub-Sahelian Africa. Technical Cooperation consultancy report (TCP/RAF/2323) by Dr. M.H. Woodford. Rome: FAO; 1984. 60 pp. [31] Mariner JC, McDermott J, de Jong M, et al. A model of lineage 1 and lineage 2 rinderpest virus transmission in pastoral areas of East Africa. Vet Microbiol 2002, in press. [32] James AD, Rossiter PB. An epidemiological model of rinderpest. I. Description of the model. Trop Anim Health Prod 1989;21:59–68. [33] Food and Agriculture Organization. Notes on rinderpest applicable to the Near East region. Information Service of the Animal Production and Health Division for the Near East, 1970. p. 1–4. [34] Hussain M, Iqbal M, Taylor WP, et al. Pen-side test for the diagnosis of rinderpest in Pakistan. Vet Rec 2001;149:300–2. [35] Littlewood W. Cattle plague in Egypt in 1903–04–05. J Comp Pathol 1907;18:312–21. [36] Barrett T, Forsyth M, Inui K, Wamwayi HM, et al. Rediscovery of the second African lineage of rinderpest virus: its epidemiological significance. Vet Rec 1998;142:669–71. [37] Roeder PL, Drew TW. Mucosal disease of cattle: a late sequel to fetal infection. Vet Rec 1984;114:309–13. [38] Stoffregen B, Bolin SR, Ridpath JF, et al. Morphologic lesions in type 2 BVDV infections experimentally induced by strain BVDV2–1373 recovered from a field case. Vet Microbiol 2000;77:157–62.

P.L. Roeder, W.P. Taylor / Vet Clin Food Anim 18 (2002) 515–547

547

[39] Gibbs EPJ, Taylor WP, Lawman MJP, et al. Classification of peste des petits ruminants virus as the fourth member of the genus Morbillivirus. Intervirology 1979;11:268–74. [40] Taylor WP, Roeder PL. In: OIE manual of standards for diagnostic tests and vaccines. 4th edition. Paris: Office International des Epizooties; 2001. [41] Libeau G, Diallo A, Colas F, et al. Rapid differential diagnosis of rinderpest and peste des petits ruminants using an immunocapture ELISA. Vet Rec 1994;134:300–4. [42] Forsyth MA, Barrett T. Evaluation of polymerase chain reaction for the detection and characterisation of rinderpest and peste des petits ruminants viruses for epidemiological studies. Virus Res 1995;39:151–63. [43] Bru¨ning A, Bellamy K, Talbot D, et al. A rapid chromatographic test for the pen-side diagnosis of rinderpest virus. J Virol Methods 1999;81:143–54. [44] Anderson J, McKay JA, Butcher RN. The use of monoclonal antibodies in competitive ELISA for the detection of antibodies to rinderpest and peste des petits ruminants. In: The seromonitoring of rinderpest throughout Africa. Phase one. Proceedings of Final Research Coordination Meeting. Vienna: Joint FAO/IAEA Division; 1991. p. 43–53. [45] Mariner JC, House JA, Mebus CA, et al. Production of a thermostable VERO cell-adapted rinderpest vaccine. Journal of Tissue Culture Methods 1991;11:253–6. [46] Mariner JC. The world without rinderpest: outreach to marginalised communities. In: Proceedings of the FAO Technical Consultation on the Global Rinderpest Eradication Programme, FAO Animal Production and Health Paper 129, Rome; 1996. p. 97–107. [47] Walsh EP, Baron MD, Rennie LF, et al. Recombinant rinderpest vaccines expressing membrane-anchored proteins as genetic markers: evidence of exclusion of marker protein from the virus envelope. J Virol 2000;74:10165–75. [48] Verardi PH, Aziz FH, Ahmad S, et al. Long-term sterilizing immunity to rinderpest in cattle vaccinated with a recombinant vaccinia virus expressing high levels of the fusion and haemagglutinin glycoproteins. J Virol 2002;76:484–91. [49] Office International des Epizooties. Recommended standards for epidemiological surveillance systems for rinderpest. Appendix 4.5.1.1. of the OIE international animal health code. 2001. p. 395–400. [50] Office International des Epizooties. International animal health code. Rinderpest. Paris: OIE; 2001. p. 81–9 [chapter 2.1.4]. [51] Food and Agriculture Organization. FAO expert consultation on the strategy for global rinderpest eradication, Rome, October 1992.