Rabies has been reported in Tanzania, mainly in the southern highland regions, since 1954. To date, rabies is endemic in all districts in Tanzania and efforts are being made to contain the disease. It was determined that mass vaccination of at least 70% of an animal population is most effective, in terms of profitability and cost, in reducing transmission of rabies. The current approach for vaccination in Tanzanian villages takes some features from the EPI method but is rather basic and unreliable. This mini-dissertation proposes using a sampling technique which incorporates the spatial component of the village data and minimises the walking distance between the sampled houses while ensuring the 70% coverage of the animal population. / Mini Dissertation(MSc)--University of Pretoria, 2017. / STATOMET The Centre for Artificial Intelligence Research (CAIR) National Research Foundation of South Africa (NRF CSUR grant number 90315) / Statistics / MSc / Unrestricted

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Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-02-21T12:43:27Z No. of bitstreams: 1 DissMCD.pdf: 3338735 bytes, checksum: a38bd4887b4213867a0c295a634f94c1 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-04-24T11:24:18Z (GMT) No. of bitstreams: 1 DissMCD.pdf: 3338735 bytes, checksum: a38bd4887b4213867a0c295a634f94c1 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-04-24T11:24:33Z (GMT) No. of bitstreams: 1 DissMCD.pdf: 3338735 bytes, checksum: a38bd4887b4213867a0c295a634f94c1 (MD5) / Made available in DSpace on 2017-04-24T11:31:33Z (GMT). No. of bitstreams: 1 DissMCD.pdf: 3338735 bytes, checksum: a38bd4887b4213867a0c295a634f94c1 (MD5) Previous issue date: 2016-08-08 / Não recebi financiamento / Although effective, current vaccinations against rabies, one of the most lethal infectious diseases in the world, present security issues of administration and production costs. In this scenario, modern biotechnology has become a source of new alternatives of great interest for vaccine production. The main antigen capable of conferring neutralizing immune response against infection by rabies virus is the glycoprotein of rabies virus (RVGP), which the production by recombinant DNA technology has been developed by researchers at the Viral Immunology Laboratory (LIV) of the Butantan Institute of São Paulo using various expression systems in Drosophila melanogaster S2 cells. One of the latest developments is S2MtRVGP-H-His cell line, obtained by stable transfection with plasmids containing cDNA from other components of RVGP and histidine tag to facilitate purification, both under control of the inducicle metallothionein promoter. This work aims to study the kinetic characteristics of cell growth and production of recombinant glycoprotein rRVGP rabies virus strain of Drosophila melanogaster S2MtRVGP-H-His, in order to evaluate the potential of a bioreactor with agitation induced by waves (Wave) for the scale-up production of rRVGP. The first stage of the study, involving batch cultures in 20 mL Schott bottle with commercial culture medium Sf900-III, allowed us to determine the optimal temperature of cultivation (28ºC), time of induction of expression (72 h), the specific growth rate ranging from 0.022 to 0,034 h-1; maximum cell density 1.82×107 cel.mL-¹ and rRVGP produced from 0.07 to 0.99 μg.mL-1. Based on these results, was started the second part of the study performed in the Single-use Wave bioreactor, involving batch cultures with 650 mL of Sf900-III, with 60% of dissolved oxygen and pH ranging without control from 6.2 to 7.0. The culture in the bioreactor showed maximum specific growth rate of 0,035 h-1, maximum cell density was 1.1×107cel.mL-¹ and RVGP produced 0.85 μg.mL-1. The production of large scale rRVGP with S2MtRVGP-H-His cells using the Wave bioreactor has shown to be viable, reproducible and with high potential to scale-up. / Embora eficazes, as vacinas atuais contra a raiva, uma das doenças infecciosas mais letais do mundo, apresentam problemas relacionados com a segurança de administração e o custo de produção. Nesse contexto, a biotecnologia moderna se torna uma fonte de alternativas inovadoras de grande interesse para produção de vacinas. O principal antígeno capaz de conferir uma resposta imunológica neutralizante contra o vírus rábico é a glicoproteína do vírus da raiva (RVGP), cuja produção por tecnologia de DNA recombinante vem sendo desenvolvida por pesquisadores do Laboratório de Imunologia Viral (LIV) do Instituto Butantan de São Paulo, utilizando vários sistemas de expressão em células de Drosophila melanogaster S2. Um dos mais recentes desenvolvimentos é a linhagem S2MtRVGP-H-His, obtida mediante transfecção estável com plasmídeos contendo entre outros componentes o cDNA da RVGP e a cauda de histidina para facilitar a purificação, ambos sob controle do promotor indutível da metalotioneína. O presente trabalho tem como objetivo o estudo de características cinéticas de crescimento celular e de produção de glicoproteína recombinante do vírus da raiva rRVGP da linhagem de Drosophila melanogaster S2MtRVGP-H-His com vistas a avaliação do potencial de um biorreator com agitação induzida por ondas (waves) para escalonamento da produção de rRVGP. A primeira etapa dos trabalhos, envolvendo cultivos em batelada em frasco Schott com 20 mL de meio de cultura comercial Sf900-III, permitiu a determinação da temperatura ideal (28ºC), o tempo apropriado de indução da expressão (72 h) e das velocidades específicas de crescimento de 0,022-0,034 h-1, densidade celular máxima de 1,82×107 cel.mL-¹ e rRVGP produzida de 0,07-0,99 μg.mL-1. Com base nesses resultados, iniciou-se a segunda parte dos trabalhos com cultivos em biorreator Wave utilizando 650 mL de meio Sf900-III, com concentração média de oxigênio dissolvido de 60% da saturação com ar e pH variando sem controle de 6,2-7,0. O cultivo no biorreator apresentou velocidade específica máxima de crescimento de 0,035 h-1, densidade celular máxima de 1,1×107 cel.mL-¹ e rRVGP produzida de 0,85 μg.mL-1. A produção da rRVGP em larga escala com células S2MtRVGP-H-His utilizando o biorreator Wave mostrou ser uma alternativa viável, reprodutível e com grande potencial de escalonamento.

Rabies is a fatal but preventable neurotropic disease of potentially all mammals. The disease is caused by lyssaviruses. Rabies is recognized as the 10th most common lethal infectious disease in the world, rendering it one of the most feared zoonotic diseases known to man. Nevertheless, rabies can be prevented by application of pre- or post exposure treatments. Rabies vaccines have been available since the time of Pasteur, more that one hundred years ago. Since, vaccine research focused on the development of safer and more effective vaccines. Topics of current interest in the field of rabies vaccinology were addressed in this study. A primary concern regarding the disease is human mortalities, in the range of 60 000, reported every year. Most of these are linked to exposure to rabid dogs. In addition, a great number of post exposure treatments are administered each year at great costs. Despite availability of efficacious biologics, several factors influence the optimal use and accessibility of these agents in the countries of interest, with cost and availability being the major contributing factors. A proven approach is mass oral vaccination of target animals, such as dogs, which indirectly infers protection to susceptible hosts, including man. Currently available vaccines present several disadvantages of use though, including issues of safety or doubtful stability. Safer but effective alternative vaccines that could be used in oral baits would be valuable. Here the use of two candidate host restricted poxvirus vaccine vectors were explored, particularly also in regard to oral innocuity. The construction, convenient isolation and use of a recombinant Lumpy skin disease virus (Neethling strain) expressing rabies virus glycoprotein in a mouse model were investigated. In addition, a recombinant Modified Vaccinia virus Ankara expressing rabies virus glycoprotein was prepared and tested as a vaccine in mice, dogs and raccoons. In both cases it was clear that the severe attenuation of these viruses did affect the efficacy of the recombinant vaccines in the non-permissive hosts. With the recombinant MVA a clear dosage effect could be shown, and equivalent humoral responses could only be attained at much higher titers of vaccine virus as with replication competent counterparts. Secondly, the cross-protection of rabies vaccines across the spectrum of lyssaviruses was addressed. Lyssaviruses can be divided into two groups based on sequence analysis and pathogenesis. Viruses belonging to the so-called phylogroup II, are the Mokola, Lagos and West Caucasian Bat viruses. Classic rabies biologics fail to fully protect against the viruses attributed to a lack of cross-neutralization. Here, cross-protection and cross-reactive immune responses induced by recombinant vaccinia viruses expressing rabies, Mokola or West Caucasian Bat virus glycoproteins, in single or dual combinations, were investigated. As expected, there was a lack of cross-protection of rabies and Mokola glycoprotein vaccines. There was also a clear lack of cross-protection of West Caucasian Bat virus glycoprotein vaccine and rabies and Mokola viruses. The dual antigen expressing vaccines did not appear to offer any additional protective effect in the tested model. The Mokola virus glycoprotein vaccines induced neutralizing antibody responses that significantly cross-neutralized Lagos Bat virus. / Thesis (PhD (Microbiology))--University of Pretoria, 2006. / Microbiology and Plant Pathology / unrestricted

Rabies is a zoonotic disease that is caused by a virus. Rabies infects domestic and wild animals, and is spread to people through close contact with infected saliva trough bites or scratches. The disease is present on nearly every continent of the world but most human deaths occur in Asia and Africa. Dogs continue to be the main carrier of rabies in Africa and Asia and are responsible for the human rabies deaths worldwide.People most at risk of rabies live in rural areas. The economic burden of rabies in the developing world takes large toll by means pre and post exposure prophylaxis treatments, cost of vaccine and other hidden costs. The study is set out to investigate the effectiveness of house-to-house rabies vaccination in Magabheni Township in KwaZulu-Natal province, a region that has experienced rabies outbreaks since 1976s. It is well-known that control of rabies at the animal source is a key to control of the disease in humans. However the main problem faced in the control of this zoonotic disease is that vaccination of dogs is not sustained, as a large percentage of dogs are not accessible. Due to some hiccups in existing strategies, there is always a significant percentage of the dog population that is not accessible. The strategy proposed and investigated is indeed labour intensive but result is a much higher percentage of dogs being accessed. In brief the observation and questionnaires as tools to generate data. The data obtained will be useful and can be considered as a strategy for rabies control in the country and probably the region

This study explored the attitudes of community members toward the Human Rabies in the Vhembe district of the Limpopo Province, South Africa. This study was underpinned by interpretative phenomenological analysis design. Data were collected using individual interviews of 20 participants and 6 focus groups consisting of six community members each. Both sets of interviews were audio recorded and transcribed verbatim. Data were analysed using interpretive phenomenological analysis framework for data analysis. Three super-ordinate themes emerged from data analysis: attitudes toward the Human Rabies, factors influencing attitudes toward the Human Rabies and tackling the Human Rabies. Results indicate that attitudes toward the Human Rabies has a direct influence on adherence to prevention and care approaches. Attitudes can be influenced by addressing training and educational needs and perceptions of prevention and care approaches. Recommendations are made to enhance adherence to prevention and care approaches for management of the Human Rabies. / Health Studies / M.A. (Health Studies)