An epidemiological model of rinderpest. II. Simulations of the behaviour of rinderpest virus in populations

Fixed parameters for different hypothetical strains of rinderpest virus (RV) and different susceptible populations are described together with details of their derivation. Simulations were then carried out in a computer model to determine the effects that varying these parameters would have on the behaviour of RV in the different populations. The results indicated that virulent strains of RV are more likely to behave in epidemic fashion whereas milder strains tend towards persistence and the establishment of endemicity. High herd immunity levels prevent virus transmission and low herd immunity levels encourage epidemic transmission. Intermediate levels of immunity assist the establishment of endemicity. The virus is able to persist in large populations for longer than in small populations. Different vaccination strategies were also investigated. In areas where vaccination is inefficient annual vaccination of all stock may be the best policy for inducing high levels of herd immunity. In endemic areas and in herds recovering from epidemics the prevalence of clinically affected animals may be very low. In these situations veterinary officers are more likely to find clinical cases by examining cattle for mouth lesions rather than by checking for diarrhoea or high mortalities.     

A model of lineage-1 and lineage-2 rinderpest virus transmission in pastoral areas of East Africa

The development of a stochastic, state-transition model of rinderpest transmission dynamics is described using parameter estimates obtained from both laboratory and participatory research. Using serological data, the basic reproduction numbers for lineage-1 rinderpest virus in southern Sudan and for lineage-2 rinderpest virus in Somali livestock were estimated as 4.4 and between 1.2 and 1.9, respectively. The model predictions for the inter-epidemic period in Sudan and Somalia (1.2 and 4.2 years, respectively) were in agreement with analysis of livestock-owner reports (1–2 years and 5 years, respectively).     

Disease properties, geography, and mitigation strategies in a simulation spread of rinderpest across the United States

ABSTRACT: For the past decade, the Food and Agriculture Organization of the United Nations has been working toward eradicating rinderpest through vaccination and intense surveillance by 2012. Because of the potential severity of a rinderpest epidemic, it is prudent to prepare for an unexpected outbreak in animal populations. There is no immunity to the disease among the livestock or wildlife in the United States (US). If rinderpest were to emerge in the US, the loss in livestock could be devastating. We predict the potential spread of rinderpest using a two-stage model for the spread of a multi-host infectious disease among agricultural animals in the US. The model incorporates large-scale interactions among US counties and the small-scale dynamics of disease spread within a county. The model epidemic was seeded in 16 locations and there was a strong dependence of the overall epidemic size on the starting location. The epidemics were classified according to overall size into small epidemics of 100 to 300 animals (failed epidemics), epidemics infecting 3 000 to 30 000 animals (medium epidemics), and the large epidemics infecting around one million beef cattle. The size of the rinderpest epidemics were directly related to the origin of the disease and whether or not the disease moved into certain key counties in high-livestock-density areas of the US. The epidemic size also depended upon response time and effectiveness of movement controls.     

Re-infection of wildlife populations with rinderpest virus on the periphery of the Somali ecosystem in East Africa

We report surveillance for rinderpest virus in wildlife populations in three major ecosystems of East Africa: Great Rift Valley, Somali and Tsavo from 1994 to 2003. Three hundred and eighty wild animals were sampled for detection of rinderpest virus, antigen or genome and 1133 sampled for antibody in sera from Kenya, Uganda, Ethiopia and Tanzania from 20 species. This was done modifying for wildlife the internationally recommended standards for rinderpest investigation and diagnosis in livestock. The animals were selected according to susceptibility and preference given to gregarious species, and populations were selected according to abundance, availability and association with livestock. Rinderpest virus, antigen and/or genome were detected in Kenya; within Tsavo, Nairobi and Meru National Parks. Serological results from 864 animals (of which 65% were buffalo) from the region were selected as unequivocal; showing the temporal and spatial aspects of past epidemics. Recent infection has been only in or peripheral to the Somali ecosystem (in Kenya). Our evidence supports the hypothesis that wildlife is not important in the long-term maintenance of rinderpest and that wildlife are infected sporadically most likely from a cattle source, although this needs to be proven in the Somali ecosystem. Wildlife will continue to be a key to monitoring the remaining virus circulation in Africa.     

The production of peste des petits ruminants hyperimmune sera in rabbits and their application in virus diagnosis

Hyperimmune sera were produced by serial inoculation of rabbits with Vero cell-adapted, sucrose gradient-purified Nigerian peste des petits ruminants virus (PPRV) isolate. Two antisera produced, neutralized the homologous PPRV but not the heterologous rinderpest Kabette "O" virus. The antisera gave strong precipitin lines with purified PPRV antigens and were used to detect PPRV and rinderpest virus antigens from ante-mortem secretions and post-mortem tissue homogenates from PPR and rinderpest virus infected goats and cattle by the agar gel precipitation tests (AGPT). The hyperimmune sera gave good titration curves with both purified Nigerian goat and the United Arab Emirate wildlife PPRV isolates in the indirect enzyme linked immunosorbent assay (ELISA). Results of indirect ELISA showed that although there were some cross reactions with the rinderpest, canine-distemper and measles viruses, at 1:100 dilution, the antisera would give a positive signal with only the homologous PPR virus.     

Etiology of the stomatitis pneumoenteritis complex in Nigerian dwarf goats.

The causative agent of stomatitis pneumoenteritis complex was isolated in domesticated goats and Vero cell culture. It was identified immunologically and morphologically as identical with the "Peste des Petits Ruminants" virus. There were cross reactions between stomatitis pneumoenteritis complex virus isolate and rinderpest virus by immunodiffusion and complement fixation tests but no cross neutralization. Goats recovered from stomatitis pneumoenteritis complex were protected against a challenge with rinderpest virus that was lethal to control goats. Ultrastructural morphology revealed intracytoplasmic and intranuclear inclusions made up of random arrays of fibrillar strands. Pleomorphic particles budded from the plasma membrane of infected cells and enveloped virions were seen extracellularly. Specific ferritin tagging was demonstrated in the stomatitis pneumoenteritis complex virus infected cells treated with homologous and peste des petits ruminants viral antibody systems but little, if any, tagging in the heterologous rinderpest system.     

A Comparison of The Viruses of Infectious Bovine Rhinotracheitis (IBR), Infectious Pustular Vulvovaginitis (IPV), and Rinderpest Part II. Plaque Assay

A plaque assay procedure was used successfully for studying the viruses of infectious bovine rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV), and rinderpest. The plaques produced by the IBR and IPV viruses were indistinguishable, but differed from those of rinderpest. The viruses were neutralized by their respective antisera as indicated by plaque inhibition. Plaques formed by the IBR and IPV viruses were inhibited by homologous and heterologous antisera but not by rinderpest antisera, while those of rinderpest were inhibited by the rinderpest antisera only.     

Note on the lessons of rinderpest control in Chad since 1935]

The policy of rinderpest control in Chad has passed through various phases over sufficiently long periods to validate certain concepts such as that of the usefulness of perifocal vaccination of populations which have not been previously vaccinated. After studying the reliability of data regarding livestock, vaccinations and pathology and after having reviewed the various types of vaccine used, it can be concluded that perifocal vaccination, even in conjunction with the systematic vaccination of young, has not enabled rinderpest to be brought under control in Chad. Only systematic livestock vaccination can control and eradicate the disease. A table illustrates the vaccination operations and monitoring systems used.     

Rinderpest Vaccination and the Incidence and Development of Trypanosomosis in Cattle

An investigation was made into whether recent vaccination of cattle with tissue culture rinderpest virus would cause immunosuppression and lead to more frequent or more severe infection with trypanosomes in animals grazing in tsetse-infested areas. Herds of cattle on Galana Ranch in Kenya were divided, with approximately half of each herd being vaccinated with tissue culture rinderpest virus strain Kabete O, while the rest remained unvaccinated. The herds were then exposed to the risk of natural infection with trypanosomes on the ranch. Three experiments were performed during different seasons. Infections with Trypanosoma congolense and Trypanosoma vivax were frequently detected but there was no evidence that vaccinated animals were more likely to acquire trypanosome infections or to show a more severe disease than unvaccinated cattle. It is concluded that tissue culture rinderpest vaccine does not cause immunosuppression and can safely be used in cattle likely to be exposed to tsetse flies and trypanosomosis.     

Identification of epitope(s) on the internal virion proteins of rinderpest virus which are absent from peste des petits ruminants virus.

Monoclonal antibodies (MAb) raised against the RBOK vaccine strain of rinderpest virus were characterized by radio-immunoprecipitation (RIPA) and in the indirect ELISA using measles (MV), distemper (CDV), rinderpest (RPV) and peste des petits ruminants viruses (PPRV). Those found to be specific for the matrix (M) protein and the nucleocapsid (N) protein could be classified into different groups on the basis of the anti-morbillivirus MAb classification scheme; a number of these MAb showed a selective recognition of RPV, measles virus and distemper virus, or of different isolates of rinderpest virus, demonstrating that greater inter-isolate variation occurs than was apparent from analyses using polyclonal antisera. One group of anti-F protein MAb (group F1) reacted with all isolates of both RPV and PPRV. A second group of anti-N protein MAb (group N1/A) reacted with all RPV isolates, but not with the PPRV isolates. Furthermore, these group N1/A antibodies reacted strongly with RPV isolates which were upon original isolation of high pathogenicity, but had a weaker reaction against the isolates of this virus which were of low pathogenicity. Thus, MAb against RPV, in particular those against the N protein offered a potential superior to that of molecular analyses for "isolate fingerprinting", the differentiation of RPV from PPRV and the discrimination between rinderpest viruses which had been, upon isolation, of either high or low pathogenicity.     

Effect of Immunization with Plasmid DNA Encoding for Rinderpest Virus Matrix Protein on Systemic Rinderpest Virus Infection in Rabbits

Plasmid vaccine pBK-CMVMP1LC113 expressing the matrix (M) gene of rinderpest virus was assessed for its potential to protect rabbits against a lethal viral challenge. Rabbits immunized with plasmids expressing the M gene were not protected when challenged with lapinized rinderpest virus, despite the production of anti-M antibodies, while rabbits immunized with rinderpest tissue culture vaccine were completely protected from a lethal challenge with lapinized rinderpest virus. The plasmid vaccine also had no significant effect on the lymphopenia in challenged rabbits. The results indicate that rinderpest M protein does not have a protective role in rinderpest infection.     

Characterisation of the European seal morbillivirus

The ELISA test originally developed for the detection of serum antibodies to rinderpest virus has been shown to detect cross-reacting antibodies in sera of diseased common and grey seals. Analysis of sera collected from various seal populations is in progress to establish the correlation between different morbillivirus neutralisation tests, ELISA tests and the disease status of the animals. RNA purified from post-mortem tissues removed from diseased seals has been analysed by hybridisation with cloned cDNAs made to various genes of canine distemper, peste des petits ruminants, rinderpest and measles viruses. This study has confirmed the presence of RNA sequences characteristic of a morbillivirus, but shown that the virus is not identical with any known morbillivirus. Work is in progress to determine the nucleotide sequences of clones carrying inserts homologous to morbillivirus genes isolated from cDNA made on a template of infected seal tissue RNA.     

Improved isolation of rinderpest virus in transformed bovine T lymphoblast cell lines.

Bovine T lymphoblast cell lines transformed by the protozoan Theileria parva were compared with bovine kidney (BK) and Vero cells for their ability to isolate various strains of rinderpest virus from tissues and infected secretions. All of the strains of rinderpest virus that were tested, including attenuated cell-culture, caprinised and lapinised vaccines, and both mild and virulent pathogenic strains, readily induced syncytial cytopathic effect (cpe) in T lymphoblasts. The cpe could often be detected within one day of inoculation of lymphoblasts, whereas it took three to 14 days to appear in Vero and BK cells. Using lymphoblasts it was possible to reisolate rinderpest virus from nine of 42 swabs collected from three cattle experimentally infected with an isolate from a recent outbreak of mild disease whereas the same swabs yielded only one reisolate on BK cells. It was also possible using the lymphoblasts to detect infectious virus in the ocular, nasal and oral secretions of goats and rabbits infected with caprinised and lapinised virus, respectively. Peste des petits ruminants virus appeared to grow as rapidly as rinderpest virus in the lymphoblasts whereas canine distemper virus readily induced cpe on first passage but less readily on subsequent passage. Measles virus induced relatively little cpe when inoculated into lymphoblasts and did not appear to passage in these cells. The lymphoblasts are easy to maintain in culture and since they rapidly recovered 11 isolates from 37 diagnostic samples could prove useful in laboratories carrying out rinderpest diagnosis.     

Diagnosis of Rinderpest in Tanzania by a Rapid Chromatographic Strip-test

A simple chromatographic strip-test based on Clearview technology, is under development as a pen-side test for the detection of rinderpest antigen in eye swabs taken from cattle in the field. An outbreak of rinderpest occurred in the northern zone of Tanzania from late February to June 1997. The affected cattle exhibited very mild clinical signs, which made clinical diagnosis difficult. One hundred and seven eye swabs were collected from cattle suspected of infection with rinderpest. These were tested in the field using a prototype of the pen-side test and 13 (12.15%) of the samples were found to be positive for the presence of rinderpest antigen. These were confirmed by ICE. The positive cases were predominantly found in the Ngorongoro district. This demonstrates the usefulness of such a simple, rapid pen-side diagnostic assay, particularly when clinically `mild' strains of rinderpest are present.     

Serological studies with the virus of peste des petits ruminants in Nigeria.

It was possible to distinguish separate serological responses when experimental goats were inoculated with either rinderpest virus or peste des petits ruminants virus. Examination of field samples established that peste des petits ruminants occur commonly in Nigerian sheep and goats although some villages have escaped recent infection. There was no evidence of infection with rinderpest in these animals.     

The risk of rinderpest re-introduction in post-eradication era

In 2011, ten years after the last reported outbreak, the eradication of rinderpest was declared. However, as rinderpest virus stocks still exist, there remains a risk of rinderpest re-introduction.     

Continuing presence of rinderpest virus as a threat in East Africa, 1983-1985

The re-emergence of rinderpest virus in East Africa in 1979 caused widespread outbreaks of disease and subclinical infection throughout the region until mid-1983. Subsequent massive emergency vaccination campaigns have been successful in eliminating clinical rinderpest from Tanzania and preventing its spread southwards. Unfortunately the virus is still endemic in north-eastern Uganda and has recently caused epidemic outbreaks with high mortality in cattle in that country. In Kenya, buffaloes (Syncerus caffer) in and around the Masai Mara game reserve have developed antibodies to rinderpest virus as recently as late 1984. Although there have been no outbreaks of clinical disease in Tanzania or Kenya from April 1983 to the end of 1985 this serological evidence plus the increasing incidence of clinical outbreaks in Uganda indicate that rinderpest virus still threatens East Africa. The substantial aid which has been provided to the region for rinderpest control must be maintained.     

A Comparison of the Viruses of Infectious Bovine Rhinotracheitis (IBR), Infectious Pustular Vulvovaginitis (IPV), and Rinderpest: Part I. Studies of Antigenic Relationships

The viruses of infectious bovine rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV), and rinderpest were compared by specific methods. The results further confirmed that IBR and IPV are caused by agents with common antigens. No antigenic relationship was found between these viruses and rinderpest virus, which confirms earlier work.     

Prevalence of antibodies to bovine virus diarrhoea-mucosal disease virus in Tanzanian cattle

A serological survey to determine the prevalence of antibodies to bovine virus diarrhoea-mucosal disease (BVD-MD) virus was conducted on 419 bovine serum samples originating from 18 of 20 regions (except Mwanza and Shinyanga) of the Tanzania mainland. The sera were a small proportion of samples collected for the appraisal of immune response to rinderpest vaccination. The survey indicated that the virus is prevalent in cattle populations and approximately 12% of sera tested contained demonstrable neutralising antibodies against BVD-MD virus.