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

Raccoon contact networks predict seasonal susceptibility to rabies outbreaks and limitations of vaccination

1. Infectious disease transmission often depends on the contact structure of host populations. Although it is often challenging to capture the contact structure in wild animals, new technology has enabled biologists to obtain detailed temporal information on wildlife social contacts. In this study, we investigated the effects of raccoon contact patterns on rabies spread using network modelling. 2. Raccoons (Procyon lotor) play an important role in the maintenance of rabies in the United States. It is crucial to understand how contact patterns influence the spread of rabies in raccoon populations in order to design effective control measures and to prevent transmission to human populations and other animals. 3. We constructed a dynamic system of contact networks based on empirical data from proximity logging collars on a wild suburban raccoon population and then simulated rabies spread across these networks. Our contact networks incorporated the number and duration of raccoon interactions. We included differences in contacts according to sex and season, and both short-term acquaintances and long-term associations. Raccoons may display different behaviours when infectious, including aggression (furious behaviour) and impaired mobility (dumb behaviour); the network model was used to assess the impact of potential behavioural changes in rabid raccoons. We also tested the effectiveness of different vaccination coverage levels. 4. Our results demonstrate that when rabies enters a suburban raccoon population, the likelihood of a disease outbreak affecting the majority of the population is high. Both the magnitude of rabies outbreaks and the speed of rabies spread depend strongly on the time of year that rabies is introduced into the population. When there is a combination of dumb and furious behaviours in the rabid raccoon population, there are similar outbreak sizes and speed of spread to when there are no behavioural changes due to rabies infection. 5. By incorporating detailed data describing the variation in raccoon contact rates into a network modelling approach, we were able to show that suburban raccoon populations are highly susceptible to rabies outbreaks, that the risk of large outbreaks varies seasonally and that current vaccination target levels may be inadequate to prevent the spread of rabies within these populations. Our findings provide new insights into rabies dynamics in raccoon populations and have important implications for disease control

Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: Fine mapping and escape mutant analysis

Anti-rabies virus immunoglobulin combined with rabies vaccine protects humans from lethal rabies infections. For cost and safety reasons, replacement of the human or equine polyclonal immunoglobulin is advocated, and the use of rabies virus-specific monoclonal antibodies (MAbs) is recommended. We produced two previously described potent rabies virus-neutralizing human MAbs, CR57 and CRJB, in human PER.C6 cells. The two MAbs competed for binding to rabies virus glycoprotein. Using CR57 and a set of 15-mer overlapping peptides covering the glycoprotein ectodomain, a neutralization domain was identified between amino acids (aa) 218 and 240. The minimal binding region was identified as KLCGVL (aa 226 to 231), with key residues K-CGV- identified by alanine replacement scanning. The critical binding region of this novel nonconformational rabies virus epitope is highly conserved within rabies viruses of genotype 1. Subsequently, we generated six rabies virus variants escaping neutralization by CR57 and six variants escaping CRJB. The CR57 escape mutants were only partially covered by CRJB, and all CRJB-resistant variants completely escaped neutralization by CR57. Without exception, the CR57-resistant variants showed a mutation at key residues within the defined minimal binding region, while the CRJB escape viruses showed a single mutation distant from the CR57 epitope (N182D) combined with mutations in the CR57 epitope. The competition between CR57 and CRJB, the in vitro escape profile, and the apparent overlap between the recognized epitopes argues against including both CR57 and CRJB in a MAb cocktail aimed at replacing classical immunoglobulin preparations

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Phenomenological MSSM interpretation of CMS searches in pp collisions at √s=7 and 8 TeV

Searches for new physics by the CMS collaboration are interpreted in the framework of the phenomenological minimal supersymmetric standard model (pMSSM). The data samples used in this study were collected at root s = 7 and 8 TeV and have integrated luminosities of 5.0 fb(-1) and 19.5 fb(-1), respectively. A global Bayesian analysis is performed, incorporating results from a broad range of CMS supersymmetry searches, as well as constraints from other experiments. Because the pMSSM incorporates several well-motivated assumptions that reduce the 120 parameters of the MSSM to just 19 parameters defined at the electroweak scale, it is possible to assess the results of the study in a relatively straightforward way. Approximately half of the model points in a potentially accessible subspace of the pMSSM are excluded, including all pMSSM model points with a gluino mass below 500 GeV, as well as models with a squark mass less than 300 GeV. Models with chargino and neutralino masses below 200 GeV are disfavored, but no mass range of model points can be ruled out based on the analyses considered. The nonexcluded regions in the pMSSM parameter space are characterized in terms of physical processes and key observables, and implications for future searches are discussed

Measurement of the integrated and differential t(t)over-bar production cross sections for high-p(T) top quarks in pp collisions at root s=8 TeV

Peer reviewe

Measurements of t(t)over-bar charge asymmetry using dilepton final states in pp collisions at root s=8 TeV

Peer reviewe