Transmission dynamics and prospects for the elimination of canine rabies

Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R<sub>0</sub>, is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal

The impact of mutation and gene conversion on the local diversification of antigen genes in African trypanosomes

Patterns of genetic diversity in parasite antigen gene families hold important information about their potential to generate antigenic variation within and between hosts. The evolution of such gene families is typically driven by gene duplication, followed by point mutation and gene conversion. There is great interest in estimating the rates of these processes from molecular sequences for understanding the evolution of the pathogen and its significance for infection processes. In this study, a series of models are constructed to investigate hypotheses about the nucleotide diversity patterns between closely related gene sequences from the antigen gene archive of the African trypanosome, the protozoan parasite causative of human sleeping sickness in Equatorial Africa. We use a hidden Markov model approach to identify two scales of diversification: clustering of sequence mismatches, a putative indicator of gene conversion events with other lower-identity donor genes in the archive, and at a sparser scale, isolated mismatches, likely arising from independent point mutations. In addition to quantifying the respective probabilities of occurrence of these two processes, our approach yields estimates for the gene conversion tract length distribution and the average diversity contributed locally by conversion events. Model fitting is conducted using a Bayesian framework. We find that diversifying gene conversion events with lower-identity partners occur at least five times less frequently than point mutations on variant surface glycoprotein (VSG) pairs, and the average imported conversion tract is between 14 and 25 nucleotides long. However, because of the high diversity introduced by gene conversion, the two processes have almost equal impact on the per-nucleotide rate of sequence diversification between VSG subfamily members. We are able to disentangle the most likely locations of point mutations and conversions on each aligned gene pair

Skeletally Dugundji spaces

We introduce and investigate the class of skeletally Dugundji spaces as a skeletal analogue of Dugundji space. The main result states that the following conditions are equivalent for a given space $X$: (i) $X$ is skeletally Dugundji; (ii) Every compactification of $X$ is co-absolute to a Dugundji space; (iii) Every $C^*$-embedding of the absolute $p(X)$ in another space is strongly $\pi$-regular; (iv) $X$ has a multiplicative lattice in the sense of Shchepin \cite{s76} consisting of skeletal maps

Failure of vaccination to prevent outbreaks of foot-and-mouth disease

Outbreaks of foot-and-mouth disease persist in dairy cattle herds in Saudi Arabia despite revaccination at intervals of 4-6 months. Vaccine trials provide data on antibody responses following vaccination. Using this information we developed a mathematical model of the decay of protective antibodies with which we estimated the fraction of susceptible animals at a given time after vaccination. The model describes the data well, suggesting over 95% take with an antibody half-life of 43 days. Farm records provided data on the time course of five outbreaks. We applied a 'SLIR' epidemiological model to these data, fitting a single parameter representing disease transmission rate. The analysis provides estimates of the basic reproduction number R(0), which may exceed 70 in some cases. We conclude that the critical intervaccination interval which would provide herd immunity against FMDV is unrealistically short, especially for heterologous challenge. We suggest that it may not be possible to prevent foot-and-mouth disease outbreaks on these farms using currently available vaccines

Spatiotemporal epidemiology of rabies at an interface between domestic dogs and wildlife in South Africa

We characterized the spatiotemporal epidemiology of rabies from January 2009 through March 2014 across the interface between a wildlife reserve and communal livestock farming area in South Africa. Brain tissue from 344 animals of 28 different species were tested for lyssavirus antigen. Of these, 146 (42.4%) samples tested positive, of which 141 (96.6%) came from dogs. Brain samples of dogs were more likely to test positive for lyssavirus antigen if they were found and destroyed in the reserve, compared to samples originating from dogs outside the reserve (65.3% vs. 45.5%; odds ratio (OR) = 2.26, 95% confidence interval (CI) = 1.27–4.03), despite rabies surveillance outside the reserve being targeted to dogs that have a higher index of suspicion due to clinical or epidemiological evidence of infection. In the reserve, dogs were more likely to test positive for rabies if they were shot further from villages (OR = 1.42, 95% CI 1.18–1.71) and closer to water points (OR = 0.41, 95% CI 0.21–0.81). Our results provide a basis for refinement of existing surveillance and control programs to mitigate the threat of spillover of rabies to wildlife populations.http://www.nature.com/srepam2019Veterinary Tropical Disease

Competition, predation, and migration: individual choice patterns of Serengeti migrants captured by hierarchical models

Large-herbivore migrations occur across gradients of food quality or food abundance that are generally determined by underlying geographic patterns in rainfall, elevation, or latitude, in turn causing variation in the degree of interspecific competition and the exposure to predators. However, the role of top-down effects of predation as opposed to the bottom-up effects of competition for resources in shaping migrations is not well understood. We studied 30 GPS radio-collared wildebeest and zebra migrating seasonally in the Serengeti-Mara ecosystem to ask how predation and food availability differentially affect the individual movement patterns of these co-migrating species. A hierarchical analysis of movement trajectories (directions and distances) in relation to grass biomass, high-quality food patches, and predation risk show that wildebeest tend to move in response to food quality, with little attention to predation risk. In contrast, individual zebra movements reflect a balance between the risk of predation and the access to high-quality food of sufficient biomass. Our analysis shows how two migratory species move in response to different attributes of the same landscape. Counterintuitively and in contrast to most other animal movement studies, we find that both species move farther each day when resources are locally abundant than when they are scarce. During the wet season when the quality of grazing is at its peak, both wildebeest and zebra move the greatest distances and do not settle in localized areas to graze for extended periods. We propose that this punctuated movement in highquality patches is explained by density dependency, whereby large groups of competing individuals (up to 1.65 million grazers) rapidly deplete the localized grazing opportunities. These findings capture the roles of predation and competition in shaping animal migrations, which are often claimed but rarely measured