Caption title: An inaugural dissertation on yellow fever. / Dedicated to Dr. Wright Post, professor of anatomy and surgery in Columbia College, and also to Dr. Isaac Ledyard, health officer, Dr. James Tillary, resident physician, and Dr. Edward Miller, health commissioner.

Caption title: An inaugural dissertation on yellow fever. / Dedicated to Dr. Wright Post, professor of anatomy and surgery in Columbia College, and also to Dr. Isaac Ledyard, health officer, Dr. James Tillary, resident physician, and Dr. Edward Miller, health commissioner. Microform version available in the Readex Early American Imprints series.

Thesis (M.S.)--Humboldt State University, 2006. / Includes bibliographical references (leaves 62-67). Also available via Humboldt Digital Scholar.

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No description available.

BACKGROUND Yellow fever (YF) is a non-contagious, mosquito borne haemorrhagic fever caused by a single-strand RNA flaviviruses. YF is endemic in the tropics primarily in South America and Africa although the vectors are present in Asia, Europe, Pacific and Middle East. Human beings serve as viraemic hosts for mosquito infection. YF carries a high burden of disease, particularly in developing countries with up to 200 000 cases reported annually and a case fatality rate of 20-50%.The pathogenesis is poorly understood and little research has been conducted .There is no known cure or specific treatment for YF and prevention remains the mainstay the public health approach in terms of effectiveness and cost. The World Health Organisation (WHO) conventions have made vaccination mandatory for travel to endemic countries to prevent outbreaks and transmission to susceptible individuals. YF vaccine is one of the oldest vaccines known and in use and is derived from an attenuated virus strain 17D originally produced in the 1930s. The vaccine has historically been considered effective and safe. However, severe life-threatening side effects to the vaccine have been reported in the past 20 years. Acute vaccinerelated viscerotropic (AVD) and neurotropic (AND) side effects have been reported globally particularly in the elderly. The adverse reactions typically present as YF- like illness resulting in multi-organ failure with death as a possible outcome. OBJECTIVES To estimate the immunogenicity and toxicity of 17D and 17DD YF vaccines by summarizing the available data from randomised controlled trials. STUDY DESIGN A summary of randomized controlled trials (RCT) of YF vaccine immunogenicity and safety and tolerability was obtained using standard meta-analysis methodologies. METHODS A comprehensive literature search was conducted in order to identify trial that met with predetermined inclusion and exclusion criteria. Features of each study were noted taking into account the type of vaccine used, the duration of follow up, assignment to intervention, blinding and randomization methods. Three studies were eventually pooled and effect size estimates reported in each study were noted and analysed using meta-analysis software, MIX. Reports on the side effects post vaccination were summarized and analysed. RESULTS The difference in outcomes between the standard 17DD YF vaccines intervention, traded as Arilvax ® and the 17D YF vaccines traded as YF-Vax ® and Stamaril ® was negligible in terms of effect size. Effect sizes that considered the means between the treatment and control groups demonstrated a difference that favoured the control group viz. Arilvax ®. The pooled results also showed significant publication bias most likely attributable to the small number of studies considered. The pooled and annotated forest plot supported the available literature in confirming the effectiveness of YF vaccines in conferring immunity. A summary of tolerability events CONCLUSIONS This study has confirmed the effectiveness of YF vaccines in terms of immunogenicity and also demonstrated that YF vaccines are well tolerated and safe The small number of study units considered in this study presented challenges for analysis and for interpretation but highlighted the need for more research to be conducted in this area. The results are in keeping with the existing body of evidence supporting the robustness of the immunological response to YF vaccination. The safety and tolerability of the vaccine established in this study was also consistent with known literature. There are important implications for further research and implementation that became evident such as the need for further studies to be conducted in African populations where the burden of disease is highest. / Dissertation (MSc)--University of Pretoria, 2010. / Clinical Epidemiology / unrestricted

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Stephen Higgs / The genetic composition of arboviruses is a critical determinant of viral infectivity and the capacity for virus dissemination in arthropod vectors. Due to concerns related to a hypothetical potential for loss of attenuation, the supression of vector infection and dissemination is a critical component for the rationale-based design of live-attenuated flavivirus vaccine candidates. The yellow fever virus (YFV) 17D vaccine virus is not only attenuated in vertebrates, but also has low infectivity for Aedes agypti mosquitoes and since it does not disseminate, it is not transmissible. Using a reverse genetics system, the mutations present in the envelope protein YFV 17D virus were characterized in Ae. aegypti to determine the role of mutations in limiting the viral infectivity and dissemination capacity. This knowledge would contribute to the rational design of live attenuated vaccines with the desirable phenotype of being nontransmissible by arthropod vectors. The upper lateral portion of the YFV 17D envelope (E) protein domain III (EDIII) habors the T380R mutation in the FG loop. Experiments demonstrated that the T380R mutation was associated with the viral infectivity phenotype for mosquitoes, but did not influence dissemination into the secondary tissues. The G52R mutation in the molecular hinge region that is located between E protein domains I (EDI) and II, significantly reduced viral infectivity for mosquitoes. In contrast, when cloned into the Asibi wildtype virus genetic backbone, the T173I mutation in the loop structure between the G0 and H0 β- strands did not attenuate viral infection and dissemination. The double mutant virus containing both the G52R and T173I mutations in the E protein, showed a similar attenuated reduced infectivity to the single G52R mutant. The M299I mutation in the linker region between EDI and EDIII resulted in a significantly lower viral infectivity at the initial phase of viral infection at 7 days post-infection in Ae. aegypti. In conclusion, the characterization on four mutations in the YFV 17D vaccine E protein have demonstrated three genetic loci, that can influence the process of YFV infection in Ae. aegypti. These results provide new knowledge and understanding which may have broad applications for the rationale design of safe flavivirus vaccines, via targeting genetic loci and introducing specific mutations that preclude infection of, and transmission by arthropod vectors.

Throughout the nineteenth century, New Orleans was repeatedly plagued by yellow fever epidemics. In this paper, cultural representations of yellow fever are considered in three novels: Baron Ludwig Von Reizenstein’s The Mysteries of New Orleans (1854-1855), George Washington Cable’s The Grandissimes (1880), and Mollie Evelyn Moore Davis’ The Queen’s Garden (1900). Because the etiology was unknown during the nineteenth century, yellow fever becomes a floating signifier on which to project the ills they observed in New Orleans society. Yellow fever thus becomes a representation of loose sexual mores, as well as a divinely retributive punishment for slavery, or a sign of adherence to an unequal, antiquated, aristocratic and un-American social system. Yellow fever, in these texts, exposes the struggles with race and racial superiority and illuminates tensions between groups of whites as New Orleans became an American city.

Thesis--Universidad de Sevilla. / "Apéndice demografico": p. 134-180. Includes bibliographical references (p. 132-134).

Thesis--Universidad de Sevilla. / "Apéndice demografico": p. 134-180. Includes bibliographical references (p. 132-134).