Orientador: José Rafael Modolo / Banca: Denise Lopes / Banca: José Paes de Almeida Nogueira Pinto / Banca: Hení Falcão da Costa / Banca: João Marcelo Azevedo de Paula Antunes / Resumo: A Raiva continua sendo uma enfermidade de preocupação mundial com severidade de ser praticamente 100% letal para as pessoas tendo o cão como seu principal transmissor. O procedimento mais eficaz para controlar a enfermidade é quando são vacinados 75% dos cães de um Município, quantidade que contribui para a interrupção do elo epidemiológico de transmissão da doença e, por consequência, proteção à saúde pública. A experiência acumulada desde 1968 em planejamentos de campanhas de vacinação anual em cães e gatos em diferentes Municípios do estado de São Paulo objetivou a elaboração do presente compêndio. Os materiais e métodos foram descritos e analisados sobre aspectos temáticos e operacionais de áreas do conhecimento sendo empreendidos como procedimentos para permitir sustentação para elaborações de políticas setoriais subsequentes. O desenvolvimento do compêndio, portanto, foi sustentado nesses 47 anos de planejamentos de campanhas de vacinação anual contra a Raiva baseando-se principalmente nas características da área e nas dinâmicas populacionais animal e humana dos Municípios alvos das campanhas, detalhando os procedimentos operacionais necessários para que a meta de vacinação dos animais possa ser atingida em cada Município, considerando-se ainda as condições socioeconômicas e culturais das áreas objetos dos planejamentos das campanhas de vacinação / Abstract: Rabies is still a concerning worldwide disease with almost 100% lethality to people and the dog acting as the main carrier. The most efficient proceeding to control the disease is when 75% of the dog population in one city is vaccinated, amount that contributes to the interruption of the disease epidemiological transmission cycle, and, by consequence, public health protection. The experience accumulated since 1968 in planning the annual vaccination campaign in dogs and cats in different cities from São Paulo state aimed the elaboration of the present compendium. Material and methods were described and analyzed under the thematic and operational aspects from areas of knowledge and undertaken as proceedings to allow sustaining to elaborate subsequential sectorial politics. The compendium development, thus, was sustained on these 47 years of annual vaccination campaign against rabies based mainly on the area characteristics and animal and human populational dynamics at the target cities detailing the operational proceedings needed so that the goal to vaccinate the animals be achieved in each city considering further the cultural and socioeconomic conditions of the areas from the vaccination campaign planning / Doutor

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Made available in DSpace on 2014-08-26T17:15:06Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 91.pdf: 7442873 bytes, checksum: 27b69519fc283b4bdd1b15559627fb79 (MD5) Previous issue date: 2009 / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde / O presente estudo é uma aplicação prática do conceito dos Três Rs (3Rs) de Russell e Burch (1959) nos ensaios de controle da qualidade de imunobiológicos para Raiva preconizados pela Farmacopéia Brasileira através de: uma análise retrospectiva de dados para a Redução do nº de animais no Ensaio de Potencia NIH para vacina contra raiva de uso humano (vaccinum rabiei ad usum humanum); mudanças no método de avaliação da inativação viral destas vacinas utilizando animais e células e validação de um ensaio in vitro para substituir o ensaio in vivo no teste de potência de imunoglobulinas anti-rábicas (Immunosera rabicum ex animali ad usum humanum e immunoglobulinum humanum rabicum). Todos os três protocolos de ensaio testados no estudo demonstraram viabilidade de utilização. / The present study is a practical application of the Russell and Burch 3Rs concept (1959) in the in vivo tests described in the Farmacopéia Brasileira for quality control of rabies biologicals by testing: A reduction in the number of mice in the NIH potency test for rabies vaccine for human use (vaccinum rabiei ad usum humanum); changes in the evaluation of virus inactivation method using suckling mice and cells as an alternative to the current Brazilian Pharmacopoeia official test (Reduction, Refinement and Replacement) and the validation of an in vitro assay to replace the in vivo assay for the potency test of Rabies Immunoglobulins (Immunosera rabicum ex animali ad usum humanum e immunoglobulinum humanum rabicum) (Replacement). All the three assay protocols have shown viability of use.

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

The lyssavirus genus of the Rhabdovirus family is divided into seven genotypes. Genotype 3, Mokola virus, has only been found on the African continent, and has been reported to infect rodents, cats, dogs and humans. The first Mokola virus identification in South Africa was made in 1970, on the east coast of the KwaZulu-Natal province. After 25 years, Mokola virus was again identified in three cats, 650 km south-west of the previous isolation. In 1997 two more Mokola infections were identified in Pinetown, only about 23 km south-west of the 1970 isolation. Phylogenetic analysis of the nucleic acid sequences of the nucleoprotein gene region of the Mokola genome, indicated that the Mokola viruses from the same geographical region were more closely related, irrespective of the time of isolation. The identification of these two distinct clusters of Mokola in South Africa leads i us to believe that this virus is more widespread than previously thought, but that the reservoir host species remains to be identified. Genotype 1 in the Rhabdovirus family, rabies virus, is found on all continents, except Australia, New Zealand, Papua New Guinea, Japan, Hawaii, Taiwan, United Kingdom, Ireland, etc. An ongoing rabies enzootic in southern Africa is associated with two genetically distinct groups of viruses, called the canid biotype (infecting carnivores of the family Canidae) and the viverrid biotype (infecting carnivores of the subfamily Viverrinae). We identified the first cases of spillover of canid biotype virus into viverrid hosts, using monoclonal antibody and nucleic acid sequence analysis. Genetic analysis of the G-L intergenic region of the rabies virus genome, showed that these spillover events do not bring about any significant change on this part of the virus genome. All of these spillover isolates maintained a typical canid virus phylogeny. Rabies viruses associated with the family Viverridae form a highly diverse group of viruses, which can be divided into four distinct phylogenetic groups, each associated with a specific geographical area in South Africa. The canid biotype of rabies virus is divided into three specific groups, based on geographic location and the associated reservoir species, namely KwaZulu-Natal province (with domestic dogs as its main vector), the western parts of South Africa (bat-eared foxes) and the northern parts of South Africa (black-backed jackals). In order to determine the degree of genetic change in the virus over a period of time, we identified two endemic canid rabies regions (KwaZulu-Natal and the northern parts of South Africa) and analysed the nucleic acid sequence variation 0f the viruses over 15 years. Phylogenetic analysis of the variable G-L intergenic region of t e virus genome indicated that the canid rabies biotype changed less than 1% over the period studied. This implies that the highly diverse viverrid biotype has been circulating in the southern African wildlife for a very long time. In order to obtain a faster, more economical, and reliable method for rabies virus biotype identification, a competitive, hemi-nested PCR assay was developed. In a single tube, two biotype specific oligonucleotides (developed by Jaftha, 1997), and a common downstream primer were -used in the biotype specific, second round amplification. The specific virus biotypes were identified on the basis of specific amplicon sizes for each biotype. A third biotype specific primer was designed to target a region of the Nucleoprotein gene, this primer was used in a second round hemi-nested reaction. Despite having been designed to specifically amplify canid biotype viruses, this primer amplified all rabies biotypes non¬specifically. We conclude that the nucleoprotein genes are too conserved to make this part of the genome a good target for a biotype-specific PCR diagnostic assay. / Dissertation (MSc (Agric) Microbiology)--University of Pretoria, 1997. / Microbiology and Plant Pathology / unrestricted

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)