1,721,000 research outputs found

    Editorial : Foot-and-mouth disease epidemiology, vaccines and vaccination : moving forward

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    Vaccination has played a major role in foot-and-mouth disease (FMD) control. There are different approaches to the design and implementation of vaccination campaigns, and epidemiological information is paramount in influencing the vaccine and vaccination strategy that best suit each geographic location. FMD-endemic regions typically organize vaccination campaigns as a routine preventive control policy or to mitigate the impact of the disease. The majority of currently used vaccines are formulated with chemically inactivated whole-viral particles and suitable adjuvants such as single and double oil emulsions. The most recent strains circulating in a particular region are typically selected as antigens based on the results of vaccine-matching data and in vitro experiments, however, predictions based on vaccine-matching approaches are usually uncertain without a live virus challenge in natural hosts combined with reliable field data. Vaccine selection and successful vaccination campaigns rely on a deep knowledge of the epidemiology of the region where these vaccines will be used, as well as access to the appropriate diagnostic tools to underpin these campaigns.Instituto de VirologíaFil: Capozzo, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Capozzo, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vosloo, Wilna. Commonwealth Scientific and Industrial Research Organisation (CSIRO) Health and Biosecurity. Transboundary Disease Mitigation. Australian Centre for Disease Preparedness; AustraliaFil: de los Santos, Teresa. United States Department of Agriculture. Agricultural Research Service. Plum Island Animal Disease Center; Estados UnidosFil: Pérez, Andrés M. University of Minnesota. Department of Veterinary Population Medicine; Estados UnidosFil: Perez Filgueira, Daniel Mariano. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Perez Filgueira, Daniel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Investigating potential factors affecting foot-and-mouth disease virus internalisation

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    Dissertation (Msc)--University of Pretoria, 2008.Foot-and-mouth disease (FMD) is a highly contagious disease caused by the FMD virus (FMDV) belonging to the Picornaviridae family. The virus affects cloven-hoofed animals and occurs as seven immunologically distinct serotypes where six of the seven serotypes occur in Africa. This fact, as well as the role of wildlife in virus maintenance, makes eradication and control of FMDV in Africa difficult. Thus, it is imperative to attain more information regarding the genetic diversity of FMD viruses prevalent on the African continent to further our knowledge of the virus as well as to enable better control strategies and the development of improved vaccines. Sufficient genetic information regarding the Leader (L) and complete capsid-coding, P1, region of serotype A and O viruses prevalent on the African continent is lacking, although the SAT isolates have been extensively characterised in the past. In this study the sequence of the L/P1-coding region was successfully determined using a genome-walking approach for a small number of A and O viruses recovered from outbreaks isolated from various species in East and West Africa over the last 33 years. Phylogenetic analysis of the P1 and capsid-coding regions 1A, 1B, 1C and 1D revealed that the African isolates grouped strictly according to serotype and geographic region which indicated the possibility of transboundary spread of the virus within East and West African countries respectively. In contrast, phylogenetic analysis of the non-structural, Lpro-coding region revealed a different tree topology compared to the capsid-coding regions for the A and O isolates with sub-grouping according to serotype and geographic regions was less apparent. The relatedness between the serotype A and O L region might be the result of genetic recombination. The inter and intratypic nucleotide and amino acid variation of the A and O isolates revealed that the most variable capsid-coding region was the externally located VP1 whilst the internally located VP4 capsid protein was the most conserved. The observed variation is in agreement with other studies and reflects the selective pressures on these proteins which either allow or prevent the occurrence of genetic changes for structural constraints or immune escape. Surprisingly, the L protease-encoding region also displayed a high degree of variation. A detailed analysis of the L/P1 amino acid alignment of the A and O isolates revealed that although the extent of variation is high in these regions, the amino acids identified in previous studies as important for FMDV structure (for the capsid-coding regions) and function were found to be conserved, indicating that the virus has adapted itself to elude the host immune response without affecting its vital functional and structural abilities. Additionally, it was observed that the amino acid residues identified as being important for FMDV attaching to the host cell receptors e.g. the RGD amino acid motif of VP1 was highly conserved for all isolates. To further investigate the FMDV-receptor interaction, RT-PCRs were developed to examine the mRNA expression level of the known FMDV receptors. The â integrins that facilitate FMDV cell entry i.e. â1, â3, â6, â8 and heparan sulphate proteoglycans (HSPG) were investigated in susceptible cell lines used for FMDV vaccine production i.e. IB-RS-2 and BHK-21. The RT-PCRs were successfully developed and optimised. The results showed that the mRNA expression levels were variable for all receptor cDNAs tested across 36 passage levels of IB-RS-2 and BHK-21 cells. No distinct differences in virus susceptibility for three FMDV strains with continuous cell passage of IB-RS-2 and BHK-21 cells at passage levels 5, 21 and 36 could be found. The information gained from this study regarding the viral L and P1 region genetic diversity, and phylogenetic analysis has indeed impacted on our understanding of FMDV African viruses. Additionally, the investigation of the FMDV receptor mRNA expression levels and virus susceptibility on two cell lines with continuous cell passage has proved a vital starting point to determine the possible receptors expressed on the surface of cells used by the vaccine production division at the ARC-OVI-TADP and forms the basis for further investigations of the FMDV receptors on the protein level and the development of a real-time RT-PCR for FMDV receptor expression.Veterinary Tropical Diseasesunrestricte

    The association between foot-and-mouth disease virus and bovine oocytes and embryos during in vitro embryo production

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    Dissertation (MMedVet (Gyn))--University of Pretoria, 2005.No other references could be found in the literature where IVP embryos, exposed to FMDV were rendered free of the virus. To the best of my knowledge this is the first report that describes the association of FMDV with IVP embryos during IVM and IVF. Also, this is the first description of a treatment protocol where IVP embryos can be cleared of infective FMDV. Washing embryos in accordance with IETS regulations was ineffective in clearing FMDV from IVP embryos when IVM and IVF were done in the presence of FMDV; however, treatment with acid as described during these experiments was effective for achieving FMDV - free IVP embryos. This work might enable the production of IVP embryos in countries where FMDV is endemic, permitting the subsequent movement of the embryos to other countries. Also, it might serve as a way of preserving genetic material from animals during an outbreak of the disease, in countries where FMD is not endemic, through the production of disease-free embryos. This work might also be of use to the wildlife industry in South Africa. If a protocol was developed for the in vitro production of game animal embryos, notably buffalo, treatment with MES could enable the production of embryos free of FMDV. This would facilitate movement of embryos from areas in South Africa where FMDV is endemic.Production Animal Studiesunrestricte

    Genetic and phenotypic characterisation of selected african foot-and-mouth disease virus isolates

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    Thesis (PhD)--University of Pretoria, 2015.Foot-and-mouth disease (FMD) is a contagious viral disease that affects cloven hoofed animals and can be economically devastating. However, vaccination can reduce the incidence of the disease when used in conjunction with other control methods. Studies described in this thesis address three aspects beneficial to the selection of vaccine seed viruses as well as improving the design of chimeric vaccines customized for use in Africa. Molecular characterization of the non-structural proteins of African FMD viruses (FMDV) can facilitate the selection of vaccine seed strains with a fitness advantage. In addition, common mutations acquired by South African Territory (SAT) serotypes on the virus surface capsid upon cell culture adaptation may be of value to the design of recombinant constructs for chimeric viruses optimized for vaccine production. Moreover, the antigenicity of a chimeric virus vZIM14-SAT2 compared to its parental virus, SAT2/ZIM/14/90, in cattle and additionally in vaccine matching assays evaluated its compatibility for future vaccine studies. Genome comparisons of the non-structural proteins for 79 African FMDV isolates from different serotypes and topotypes, spatially and temporally dispersed, showed that critical functional motifs were conserved and variation occurred away from enzymatic active sites. The southern African FMDV clustered separately from the other African viruses on phylogenetic analysis. This increased the molecular understanding of FMDV, aiding in the selection of vaccine seed strains. The BHK-21 cell line (preferred for vaccine production) was used to serially passage eleven SAT1 and four SAT2 FMDV. This resulted in Arg or Lys mutations in the VP1 capsid protein surrounding the 5-fold axis, at positions 84-85 and 111-112 respectively. Arg at position 112 was favoured in the binding of a heparin moiety onto a SAT1 model using molecular docking simulations. This knowledge can be applied to recombinant constructs for the generation of chimeric viruses that adapt rapidly to BHK-21 cell culture for vaccine production. Vaccines derived from chimeric viruses present a good prospect in the control of FMD. The antigenic nature of an intra-serotype chimeric virus, vZIM14-SAT2, consisting of the capsid-coding region of SAT2/ZIM/14/90 in a genome-length clone pSAT2, was compared to that of its parental virus. In cattle both chimeric and parental viruses elicited similar neutralizing antibody responses and provided protection against clinical disease following homologous virus challenge. In addition, antigenic matching resulted in comparable cross-reaction results for both chimeric and parental viruses. Therefore, when used as vaccines, the antigenic profiles of chimeric viruses against SAT2 isolates did not differ from parental viruses and could be used as an alternative in vaccine production combined with the advantage of including suitable mutations for cell culture adaptation. These findings increase our knowledge on the genome structure and replication of the FMDV in BHK-21 cells. The data can be used to facilitate selection of vaccine seed viruses specific to serotype and topotype. Additionally, the information can supplement the design of recombinant constructs for chimeric vaccines for future application. Taken together, these new data broaden our options to control FMD in Africa using tailor made chimeric vaccines.tm2015Veterinary Tropical DiseasesPhDUnrestricte

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Evaluation of cross protection by an attenuated African swine fever virus isolate against heterologous challenge

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    Dissertation (MSc)--University of Pretoria, 2012.African Swine Fever Virus (ASFV) is an Asfivirus and is the only member of the family Asfarviridae. It manifests as a disease that varies from acute to sub-acute or chronic forms. A true carrier state in domestic pigs is unknown but chronically affected individuals may carry and spread the virus for extended periods. African Swine Fever (ASF) is a socio-economically important disease characterized by high morbidity and mortality affecting the livelihood of many small to big scale farmers and seriously compromising international trade. Strategic measures to control this disease are by physical containment and culling in outbreak situations. There is no vaccine available. Nevertheless, every pork producer should ideally be actively involved in having biosecurity measures in place to avoid contamination and contacting their veterinary services in case of suspicion of ASF to have appropriate samples analysed. Official veterinary services must be equipped with proper diagnostic tools in order to provide a quick response. The sensitivity of currently available diagnostic tests at the Transboundary Animal Diseases Programme, Onderstepoort Veterinary Institute was analysed in order to report the best technique available. Sensitivity to ASF virus infection and therefore diagnostic potential of cell primary cultures as bone marrow macrophages, blood macrophages and alveolar macrophages was done via comparison of titre results from inoculations of ASFV SPEC 257 as control, and ASFV MOZ 1/98. In addition, molecular detection of specific DNA fragments within the viral genome were compared using five different PCRs. Bone marrow macrophage cultures and blood macrophage cultures were the most reliable cells whereas alveolar macrophages more often showed contamination. Results show that PPA PCR and real time PCR detected the highest diluted samples, thus the lowest concentration of virus, in both trials done with ASFV MOZ 1/98 and ASFV SPEC 257. In addition, animal trials were performed by inoculating domestic pigs with four different ASFV isolates of varying pathogenicity. These viruses were all from distinct geographic origins. Non-virulent ASFV OURT 3/88 and high virulent ASFV BENIN 1/97 were previously described and used as reference viruses. ASFV MOZ 1/98, suspected of having high virulence and ASFV MKUZE, which was thought to be of low virulence were included in this study to provide further information on the pathological and clinical outcome of the disease as well as measuring viral replication in various organs and blood. The study showed that ASFV MKUZE was of intermediate virulence, whilst ASFV MOZ 1/98 was highly virulent with a high mortality rate. Results confirmed the inadequacy of ASFV MKUZE to act as vaccine opposed to ASFV OURT 3/88. Following this, a potential vaccine by use of attenuated Portuguese ASFV OURT 3/88 tested against virulent heterologous challenge with a strain now known with certainty to cause acute ASF, the isolate ASFV MOZ 1/98 collected from a diseased pig in Mozambique. Domestic commercial pigs where submitted to either one or two vaccinations before challenge. Viral load in blood and tissue samples was higher in unvaccinated animals and higher in single vaccinated than in pigs vaccinated twice. However, acute ASF afflicted all groups with severe clinical signs and post-mortem lesions. Although it did not confer total immunity it was determined that pigs vaccinated with European attenuated ASFV OURT 3/88 acquired partial protection against challenge with virulent southern Africa ASFV MOZ 1/98.gm2014ab2015Veterinary Tropical Diseasesunrestricte

    The 3A non-structural-protein coding region of the southern African SAT type isolates differs from that of other foot-and-mouth disease viruses

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    The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat v.9 was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.The 3A non-structural protein of foot-and-mouth disease viruses is a relatively conserved protein comprising 153 amino acids. Recent studies have demonstrated correlation between mutations in the 3A non-structural-protein-coding region, including a 10-amino acid deletion, and attenuation of the viruses in cattle. Although the 3A coding region of several type A, O and C isolates has previously been described, nucleotide sequence data of the 3A coding region of the South African Types (SAT) 1, 2 and 3 viruses are limited. Therefore, the 3A non-structural-coding region of different SAT serotypes was determined, analysed and compared to that of European, South American and Asian isolates. The 3A regions of the SAT isolates investigated differed markedly from that of types A, O, C and Asia-1, but were similar within the group.mn201

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Serological response of cattle vaccinated with a bivalent (SAT 1 and SAT 2) foot-and-mouth disease vaccine in Gaza Province, Mozambique

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    Dissertation (MSc)--University of Pretoria, 2012.Foot-and-mouth disease (FMD) is a viral disease endemic in Africa, the Middle East, South America, Asia and parts of Eastern Europe. It is a major constraint to international trade in livestock and livestock products in many African countries. In southern Africa, African buffaloes (Syncerus caffer) are reservoirs of the South African Territories (SAT) 1, SAT 2 and SAT 3 FMD viruses, and cattle raised in the vicinity of wildlife conservation areas are at constant risk of becoming infected with FMD viruses. In Mozambique, control of FMD is fundamentally based on vaccination of cattle in zones around protected areas. However, the vaccination protocol recommended by the vaccine producer (two primary vaccinations followed by four- to six-monthly boosters) is logistically impractical and financially not suitable for most countries. As a result, the double primary vaccination is usually not implemented. A commercially available bivalent FMD vaccine, containing the SAT 1 and SAT 2 serotypes, was assessed for its ability to induce and sustain immunity in cattle for at least 6 months following a single primary inoculation. The study was conducted with cattle reared in Limpopo National Park (LNP), Mozambique, and adjacent areas. One hundred and seventy five seronegative cattle aged between 6 and 18 months were vaccinated and 42 others from the same areas were left unvaccinated, as controls. A group of 39 vaccinated cattle were revaccinated 4 months after initial vaccination and 63 others were revaccinated 6 months after initial vaccination. The vaccinated and unvaccinated cattle were bled at predefined intervals (at vaccination, and at 1, 4, 5, 6, 8, 10 and 12 months post vaccination) and sera were tested with a liquid phase blocking ELISA to measure the antibody level against FMD virus. A high proportion (73%) of vaccinated cattle had seroconverted (log10 titre ≥1.6 for any SAT serotype) at one month after vaccination with a single primary dose and there was no significant difference between the proportions of animals that seroconverted to SAT 1 compared to SAT 2. A higher proportion of animals within LNP (82%) than outside LNP (50%) had seroconverted at one month after vaccination (P = 0.001). Overall, however, only relatively few animals (27% for SAT 1, 35% for SAT 2 and 7% for SAT 3) had protective antibody titres (log10 titre ≥2). At 4 months after vaccination, a very low proportion (8.3%) of vaccinated cattle had antibody titres ≥1.6 to any of the SAT serotypes, and there was no significant difference between the proportions of animals with antibodies to SAT 1 (2.1%) compared to SAT 2 (7.3%) (P = 0.17). No cattle had a protective titre (≥2) to SAT 1 at 4 months and only 4.2% to SAT 2. The revaccination at 4 months after initial vaccination elicited antibody titres ≥1.6 in 22% of vaccinated animals at one month after revaccination; this rose two months later to 90% and remained high (91%) at 10 months post first vaccination before dropping to 65% at 12 months. However, only 15% of cattle had protective titres (≥2) to any of the SAT serotypes at 12 months. For cattle revaccinated at 6 months after first vaccination the percentage of cattle that had a titre ≥1.6 two months after revaccination was also high (80%), remained high (89%) at 10 months post first vaccination and dropped to 54% at 12 months after first vaccination. Only 11% of cattle had protective titres (≥2) at 12 months. The research findings indicate that, although the vaccine is able to induce production of antibodies against SAT 1 and 2 in a significant percentage of cattle within one month after a single primary vaccination, these antibodies are short lived and have largely disappeared by 4 months post vaccination. This suggests that a protocol of a single primary vaccination is inadequate in naïve animals, even if revaccination takes place four months later. Revaccination improved the immune response for a longer period, resulting in detectible titres in the majority of animals for 6-8 months post revaccination. This can be used in disease control programmes to ensure some protection of cattle particularly when it is applied immediately before identified high risk periods of occurrence of FMD outbreaks. However, it seems unlikely that six-monthly revaccination is sufficient to maintain adequate levels of protective immunity. The study highlighted several difficulties associated with the vaccination of livestock under field conditions and the conduction of field trials. These included difficulties with cold chain maintenance, poor infrastructure for animal handling, and loss of follow-up due to loss of animal identification or poor owner/herder compliance. CopyrightProduction Animal Studiesunrestricte
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