title: Morbillivirus infections in animal hosts of the Serengeti District of Northern Tanzania: PPRV and CDV in multi-host livestock communities, and CDV in African wild dogs (Lycaon pictus).
Creators: name: Pomeroy-Arthur, Ursula Ellen
Publisher: name: University of Glasgow
Year: 2023

description: Morbilliviruses are responsible for some of the most devastating outbreaks of disease in animals, accompanied by high morbidity and mortality rates. Canine distemper virus (CDV) and peste des petits ruminants virus (PPRV) are highly promiscuous morbilliviruses which have widely expanded their host range in recent decades. However, the extent of infection in atypical hosts and the genetic impact upon endangered, vulnerable species remain poorly understood, particularly in East Africa. The development of a highly accurate serological method capable of differentiating between circulating morbilliviruses is required. Further, the need for longitudinal and clinical monitoring of animals is essential to understand the infection dynamics occurring in susceptible and emerging hosts. Finally, there is a lack of research on the impact which decades of morbillivirus outbreaks have had on the critically endangered African wild dogs of Tanzania, which is paramount to understanding how this species can be further protected and preserved. This thesis comprises two studies. The first study aims to confirm the presence of PPRV and CDV in cattle, sheep, and goats from ten households across the Serengeti District in Northern Tanzania. This work involves a longitudinal serological study underpinning active infection of animals, using a pseudotyped-virus neutralization assay (PVNA) to detect highly specific antibodies to PPRV and to CDV. This study also monitored clinical signs to investigate the disease manifestations of infections in livestock hosts, using a logistic regression model to test for associations between infection and signs of disease in each species. The second study aims to clarify whether genetic change has occurred in the wild dog population of the Serengeti over recent decades, by investigating neutral (microsatellite) and adaptive (MHC DRB1) genetic markers from published data (Marsden et al, 2012), and recently developed data following a fatal CDV outbreak in 2017. It also aims to determine whether there is evidence of natural selection on adaptive markers, and evidence of genetic variation attributable to factors beyond demographic change. Results from these studies demonstrate that cattle in a mixed livestock setting become naturally infected with PPRV with no associated clinical disease. Data also show for the first time that cattle, sheep, and goats become naturally infected with CDV with no associated clinical disease. CDV seropositivity was detected predominantly in cattle. Infections occurred throughout the study with no patterns associated between household and infection, indicating widespread circulation of both viruses beyond the household level. The source of infection remains to be established, although livestock trade and sporadic outbreaks in domestic dogs are likely sources of PPRV and CDV infection, respectively. This work provides strong evidence that PPRV sub-clinically infects cattle in multi-host livestock communities, and that CDV sub-clinically infects livestock, predominantly cattle. This thesis provides the first analysis of genetic changes in the Serengeti population of African wild dogs. This work utilized the pseudotype-based virus neutralization assay to detect CDV-specific neutralizing antibodies in sera of wild dogs which survived the 2017 CDV outbreak, while RT-qPCR was used to detect CDV in tissue samples from deceased wild dogs. Results showed an overwhelming proportion of PCR positives and lack of protective immune response in deceased and surviving animals, respectively. Allele frequency data showed fluctuations in DRB diversity over time coinciding with CDV outbreaks. Heterozygosity varied for both neutral and immune markers over time but showed no excess or evidence of population bottleneck. Bayesian analysis of microsatellites found some genetic structuring over time (K = 2). The test for selection indicated balancing selection during at least two time points at the DRB, in keeping with CDV outbreaks. This study provides strong evidence of population structuring and the potential link between adaptive markers and disease outbreaks in wild dogs.