Atypical bovine morbillivirus infections in the Serengeti ecosystem

Once the scourge of European, African and Asian livestock and wild ruminants, rinderpest virus is only the second virus in history after smallpox to be eradicated globally by vaccination. Rinderpest virus (RPV) is a morbillivirus, a close relative of measles virus (MV). Rinderpest was a devastating disease, threatening both food security and the health and wellbeing of many of the poorest livestock-dependent communities in the world. The eradication of rinderpest was arguably one of the most significant global successes in veterinary medicine.

In recent years, we have developed highly sensitive and specific diagnostic tests with which we can measure morbillivirus-specific neutralising antibodies. Using these tests, we have identified sera from cattle in Northern Tanzania that display specific neutralising activity against novel cattle morbilliviruses, including canine distemper virus (CDV), peste des petits ruminants virus (PPRV) and a rinderpest-related bovine morbillivirus.

The aim of this project is to characterise novel and atypical bovine morbilliviruses circulating in Northern Tanzania. We will build upon our preliminary screening of cattle sera, focussing on a set of ~5000 cattle sera from neighbouring areas of Serengeti and Ngorongoro districts. Collected between 2010 and 2016, these sera will provide a snapshot of the prevalence of morbillivirus-specific antibodies across the region and will enable us to locate target sites for future field studies. Informed by our findings, we will collect fresh sample material from herds in villages known to harbour antibody-positive animals, generating material for virus characterisation as well as allowing assessment of their clinical significance. The samples will be screened to identify the animals with morbillivirus-specific antibodies and the corresponding blood samples and swabs screened for viral gene sequences. These analyses will reveal the origin of the antibody reactivity, the nature of the infective agent and will permit the design of a more effective diagnostic test for the virus(es).

This project will provide epidemiological and biological data to evaluate the potential threat posed by morbilliviruses in cattle. It will generate assay systems with which the viruses may be detected and inform strategies for subsequent monitoring and control. The knowledge generated by this project will counter the risk of a novel morbillivirus emerging in cattle, ensure that immunosurveillance for morbilliviruses is not undermined by misdiagnosis, while facilitating the design of future campaigns for control and eradication by vaccination.

In 2015, we initiated a project to develop improved serological assays for animal morbilliviruses, assays that would be rapid and sensitive, and which would permit the distinction of diverse lineages and species of virus. The pseudotyped virus neutralisation assay (PVNA) that we developed revealed that canine distemper virus (CDV) and peste des petits ruminants virus (PPRV) were co-circulating in African livestock, wild ruminants and carnivores. During these studies, we identified samples from cattle that contained rinderpest virus (RPV)-specific antibodies. Given that the samples were collected ~12 years after the cessation of rinderpest vaccination, these findings suggest that an RPV-related bovine morbillivirus persists in the region and that multiple morbilliviruses are co-circulating in cattle.

The rinderpest eradication program was cognisant of the need for vigilance post-eradication and proposed that continued immunosurveillance would be required to prevent viral re-emergence. In this project, we will investigate the nature of the morbillivirus seropositivity in cattle. We will conduct a comprehensive serological survey of cattle across Northern Tanzania, screening for the presence of morbillivirus neutralising antibodies. Informed by these analyses, we will revisit the sites of seropositivity, collecting fresh biological specimens for additional serology and nucleic acid preparation, assessing the clinical significance of infection. Samples from confirmed seropositive animals will be used for molecular analyses, including paramyxovirus-specific quantitative PCR and deep sequencing and screening for novel viral genomes. The data generated from these analyses will enable an in-depth characterisation of the molecular, biological and clinical properties of the bovine morbilliviruses. We will ascertain the nature of the RPV-related morbilliviruses and develop bespoke PVNA-based diagnostics that will underpin enhanced immunosurveillance and vaccine development.

Eradicating morbilliviruses of livestock: The FAO/OIE program to eradicate PPRV is a substantial global undertaking and millions of doses of vaccine have already been administered in Tanzania alone. Determining whether to target small ruminants only for vaccination, or whether cattle herds in neighbouring areas require to be vaccinated is a major unresolved issue. In rural Africa, cattle generally live longer than sheep and goats. Hence if cattle or other atypical host species act as viral reservoirs, sheep and goats will require repeated programs of vaccination to ensure that "herd immunity" is maintained at a sufficient level to prevent re-emergence of the virus in an immunologically naïve host population. With the co-circulation of PPRV with RPV-related morbilliviruses and canine distemper virus (CDV) in livestock and wildlife species, the potential for mis-diagnosis and ineffective vaccination is enormous. For example, an animal with prior exposure to an RPV-related morbillivirus may resist effective vaccination with an attenuated PPRV vaccination and hence be susceptible to infection when exposed to a virulent, wild-type strain of virus.
To combat such eventualities, vaccines may need to be administered to a broader range of species, or at an increased frequency of vaccination. Such extensions of existing programmes will have significant implications for the logistics of vaccine manufacture and administration. Informed decision making based on accurate diagnosis will save time, reduce costs and enhance the likelihood of success.

Animal morbillivirus vaccine development and efficacy studies: The continued circulation of morbilliviral species that are more resistant to neutralisation or which are missed by existing diagnostic tests may interfere significantly with the effectiveness of a vaccination campaign. This project will define the species of virus currently in circulation, give an accurate estimate of prevalence and provide sequence data for vaccine refinement should it prove necessary. The high sensitivity and specificity of our serological testing will greatly enhance pre- and post-vaccination sero-surveillance, demonstrating the disease-free status of livestock and the absence of infection in wildlife reservoirs.

Livestock-keeping families in affected areas: Morbilliviruses have a significant impact on herd health and productivity in developing countries. For example, there are ~37.4 million PPR-associated sheep and goat deaths each year with an annual loss of between $1.4 billion and $2.7 billion. The accurate identification of the nature of the morbilliviruses circulating in livestock will enable livestock-keepers to protect their herds more effectively and to make informed decisions about when to vaccinate, when to boost and how to avoid re-infection. Hence, livelihoods will improve and local food sources will be protected. A better understanding of virus transmission and maintenance will have additional far-reaching benefits. It will enable veterinarians and veterinary officers to communicate with livestock keepers more effectively, to explain the rationale behind vaccination as a means of eradicating disease, how this will increase productivity and benefit the community. In doing so, this will encourage better engagement with eradication programs.

Morbilliviruses as a threat to global wildlife: Our existing direct contacts with wildlife veterinarians, conservation societies and biologists have revealed that morbilliviruses present significant threats to global wildlife populations. CDV and PPRV epizootics have affected diverse species, for example gazelle, antelope, camels and buffalo have succumbed to PPRV, while CDV continues to target endangered carnivores. The co-circulation of RPV-related viruses, PPRV and CDV in wildlife may provide a reservoir of morbilliviruses capable of invading a vacated niche in livestock post-RPV eradication, or in future years post-PPRV eradication.