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There is a need for innovation to improve control of all Neglected Zoonotic Diseases (NZDs). The Global Alliance for Rabies Control was formed to prevent human deaths from rabies and relieve the burden of rabies in other animal populations, especially dogs. It aims to identify reasons for the neglect of rabies in developing countries and to develop strategies to improve rabies control. Through initiatives such as World Rabies Day and the Partners for Rabies Prevention, progress has been made towards increased awareness of the burden of rabies transmitted by dogs at scales from local to international. An evidence base of the feasibility of canine rabies elimination has been built up and now easier access to information and tools enables countries to design and implement rabies elimination strategies in a logical way, utilizing the structures of regional networks for rabies control. The body of evidence has built consensus amongst international stakeholders in rabies control and is now being used to encourage international policy change, attract investment and increase delivery of effective rabies control programmes in canine rabies endemic countries. [ABSTRACT FROM AUTHOR]

Abstract: Towards understanding the molecular epidemiology of a severe dog rabies epidemic in the KwaZulu Natal province of South Africa, we analyzed a variable 592 nucleotide genome sequence domain of 170 rabies viruses from KwaZulu Natal and surrounding regions. Viruses from the KwaZulu Natal and Eastern Cape provinces belonged to a unique lineage, circulating as two independent and expanding epidemiological cycles. The first presented as closely related dog cycles along the eastern coastal regions of the two provinces, while the second, in northern KwaZulu Natal, has entered into at least one wildlife reservoir, the black backed jackal. We underline the success and opportunism of rabies in southern Africa, in a likely reflection of the emergence and radiation of rabies in new host species and locales throughout the larger continent as a whole. [Copyright &y& Elsevier]

Since adopting the National Biotechnology Strategy in 2001, the South African government has established several regional innovation centres and has put in place initiatives to encourage international partnerships that can spur internal development of life science ventures. This strategy seeks to capitalize on the high quality of research carried out in public research institutions and universities but is hampered, somewhat, by the lack of entrepreneurial culture among South African researchers due to, among other reasons, the expenses involved in registering foreign patents. Although private sector development is still relatively embryonic, start-ups are spinning out of universities and pre-existing companies. These represent a vital source of innovations for commercialization in the future, provided that the challenges facing the emerging South African biotechnology industry can be overcome. [Copyright &y& Elsevier]

Abstract: Oral rabies vaccination of target reservoir species has proved to be one of the pillars of successful rabies elimination programs. The use of live attenuated rabies virus vaccines has been extensive but several limitations hamper its future use. A recombinant vaccinia-rabies vaccine has also been successfully used for the oral vaccination of several species. Nevertheless, its lack of efficacy in certain important rabies reservoirs and concerns on the use of this potent live virus as vaccine carrier (vector) impair the expansion of its use for new target species and new areas. Several attenuated and host-restricted poxvirus alternatives, which supposedly offer enhanced safety, have been investigated. Once again, efficacy in certain target species and innocuity through the oral route remain major limitations of these vaccines. Alternative recombinant vaccines using adenovirus as an antigen delivery vector have been extensively investigated and may provide an important addition to the currently available oral rabies vaccine repertoire, but are not the primary subject of this review. [Copyright &y& Elsevier]

Current passive surveillance data for canine rabies, particularly for the regions where the burden is highest, are inadequate for appropriate decision making on control efforts. Poor enforcement of existing legislation and poor implementation of international guidance reduce the effectiveness of surveillance systems, but another set of problems relates to the fact that canine rabies is an untreatable condition which affects very poor sectors of society. This results in an unknown, but potentially large proportion of rabies victims dying outside the health system, deaths that are unlikely to be recorded by surveillance systems based on health center records. This article critically evaluates the potential sources of information on the number of human deaths attributable to canine rabies, and how we might improve the estimates required to move towards the goal of global canine rabies elimination. [ABSTRACT FROM AUTHOR]

Abstract: Rabies remains a global public health problem but increasingly so in the developing world. Given a lack of awareness, priority and diagnostic capability, very few developing countries, especially in Africa, report on laboratory confirmed human rabies cases. Here we present a retrospective study on the epidemiology of human rabies in Republic of South Africa for a 25-year period, 1983–2007, based on laboratory confirmed cases. The study highlights the role of the domestic dog as a reservoir and vector of rabies and contrasts this to the almost negligible contribution of wildlife vectors to the overall burden of human rabies in dog rabies endemic areas. From the collective data set, epidemiological aspects that include various features of these human rabies cases as well as failures in or towards the treatment of exposures are reported. Molecular analysis of virus isolates did not identify any additional cases of rabies attributed to infection with the Duvenhage, Lagos bat or Mokola or any other rabies-related viruses. [ABSTRACT FROM AUTHOR]

Abstract: The inflexibility of existing serological techniques for detection of rabies in surveillance constrains the benefit to be gained from many current control strategies. We analysed 304 serum samples from Tanzanian dogs for the detection of rabies antibodies in a pseudotype assay using lentiviral vectors bearing the CVS-11 envelope glycoprotein. Compared with the widely used gold standard fluorescent antibody virus neutralisation assay, a specificity of 100% and sensitivity of 94.4% with a strong correlation of antibody titres (r =0.915) were observed with the pseudotype assay. To increase the assay''s surveillance specificity in Africa we incorporated the envelope glycoprotein of local viruses, Lagos bat virus, Duvenhage virus or Mokola virus and also cloned the lacZ gene to provide a reporter element. Neutralisation assays using pseudotypes bearing these glycoproteins reveal that they provide a greater sensitivity compared to similar live virus assays and will therefore allow a more accurate determination of the distribution of these highly pathogenic infections and the threat they pose to human health. Importantly, the CVS-11 pseudotypes were highly stable during freeze–thaw cycles and storage at room temperature. These results suggest the proposed pseudotype assay is a suitable option for undertaking lyssavirus serosurveillance in areas most affected by these infections. [Copyright &y& Elsevier]

Abstract: Modified vaccinia virus Ankara (MVA) has become a vaccine vector of choice for recombinant vaccine development. A MVA-based rabies vaccine would be advantageous for use as a vaccine for dogs (and wildlife), particularly if it proves innocuous and efficacious by the oral route. Here, the generation and immunological testing of a recombinant MVA expressing a rabies virus glycoprotein gene is described. In a murine model, higher dosages of recombinant MVA were needed to induce equivocal immune responses as with Vaccinia Copenhagen or Vaccinia Western Reserve recombinants, when administered by a parenteral route. The MVA recombinant was not immunogenic or efficacious when administered per os in naïve mice. The ability of the recombinant MVA to induce anamnestic responses in dogs and raccoons was also investigated. Recombinant MVA boosted humoral immune responses in these animals when administered peripherally, but not when administered orally. [Copyright &y& Elsevier]