West Nile virus has become a major risk to humans since its first appearance in New York City in 1999. Physicians and state health officials are interested in new and more efficient methods for monitoring disease spread and predicting future outbreaks. This study modeled habitat suitability for mosquitoes that carry West Nile virus. Habitat characteristics were used to derive risk maps for the entire state of Mississippi. Statistical significance tests yielded objective evidence for choosing among many habitat variables. Variables that were significantly correlated with diagnosed human cases for 2002 were combined in weighted linear algebraic models using a geographic information system (GIS). Road density, slope, and summer precipitation minus evaporation (P-E) were the most significant variables. GIS-based model results were compared with results from logistic regression models. The algebraic model was preferred when validated by 2003 human cases. If adopted, GIS-based risk models can help guide mosquito control efforts.

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<p>The incidence and severity of infectious diseases increases in elderly people (>60 years of age). It is believe that the age-associated changes in the immune system, termed immunosenescence, lead to diminished effectiveness of the immune system leaving the aged susceptible to infectious pathogens and associated diseases. The limited efficacy of the currently available vaccines in elderly populations contribute immensely to the frequency of infectious diseases in the globally growing aging population. As such, the demographic shift warrants the development of effective prophylactic vaccines for the elderly.</p> <p>West Nile virus (WNV) became endemic in North America in 1999, and although it infects people of all ages, the incidence of severe neuroinvasive disease is more prevalent in the elderly. I hypothesized that the susceptibility of the elderly towards severe WNV disease is a consequence of aberrant immune function, and specifically lack of functional virus-specific CD8+ T cells. Contrary to my hypothesis, I found that the magnitude, breadth and functionality of WNV-specific CD8+ T cells were not different between the age cohorts. These results argue that advanced age does not limit the development of functional CD8+ T cell responses following primary infections with an acute virus. Furthermore, the aged members of our cohort maintained functional CD8+ T cells to cytomegalovirus (CMV) and Epstein-Barr virus (EBV), common persistent viruses.</p> <p>Collectively, my results demonstrate that development of vaccines designed to elicit CD8+ T cell immunity may be warranted for elderly individuals and perhaps live vectors should be considered for this population.</p> / Doctor of Philosophy (Medical Science)

WN virus has spread for over 60 years creating endemic and epidemic areas throughout Africa, Asia, and Europe, affecting human, bird, and equine populations. Its 1999 appearance in New York shows the ability of the virus to cross barriers and travel great distances, emerging into new territories previously free of infection. Spreading much faster than expected, WN virus has infected thousands of birds, equine, and humans throughout the conterminous United States (US). Case and serological studies performed in the Eastern hemisphere prior to 1999 offer detailed descriptions of endemic and epidemic locations in regards to geography, land cover, land use, population, climate, and weather patterns. Based on the severity of WN activity within each study area, the patterns associated with these environmental factors allow for the identification of values associated with different levels of risk. We can then model the landscape of the disease within the US and identify areas of high risk for infection. State and county public health officials can use this model as a decision-making tool to allocate funding for disease prevention and control. Dynamic factors associated with increased transmission, such as above average temperature and precipitation, can be closely monitored and measures of prevention can be implemented when necessary. In turn, detailed information from higher resolution analyses can be documented to an online GIS (Geographic Information System) that would contribute to a global collaboration on outbreaks and prevention of disease. / Master of Science

Field studies were conducted in southwestern Virginia to determine the bionomics and ovipositional preferences of Culex restuans Theobald and Culex pipiens Linnaeus using ovitraps and gravid traps. Both species have been implicated as enzootic and epizootic vectors of West Nile virus (WNV) and these studies provide information on the relative abundance of gravid mosquitoes. Ovitraps were used in the summers of 2002 and 2003 to measure the oviposition activity of Culex mosquitoes, mainly Cx. restuans and Cx. pipiens. In 2002, 1,345 egg rafts were collected from 5 traps set at different locations in the New River Valley (NRV). Cx. restuans constituted 93.2% of the catch; the remainder was Cx. pipiens (6.7%) and Cx. salinarius (<1%). In 2003, 4 ovitraps were placed at each of 6 locations in the NRV. Of 9,794 egg rafts collected, Cx. restuans comprised 92.8%, Cx. pipiens 6.5%, and Cx. salinarius <1%. Oviposition patterns were similar in both years. Cx. restuans oviposition was detected about mid-May, and raft numbers were highest in late June and the middle of July and then showed a steady decline throughout the remainder of each season. Cx. pipiens oviposition activity began later in the season and gradually increased, reaching its peak in August. Although the number of egg rafts of Cx. restuans decreased in August and September while the number of Cx. pipiens egg rafts increased, a crossover in the relative abundance of the two species never occurred. In 2003, the attractiveness of four infusions (cow manure, straw, grass, and rabbit chow) were compared in oviposition traps. For Cx. restuans, the manure infusions collected more egg rafts than the other three infusions for the first four weeks, with two of the weeks showing significance. During week 1, the manure infusions collected significantly more egg rafts than straw (P<0.01), grass (P<0.01), and rabbit (P<0.001). During week 2, manure collected more than grass (P<0.05) and rabbit (P<0.01). The straw and grass infusions yielded the most egg rafts after week 2, and only three weeks showed any significance. When traps began to collect Cx. pipiens, the majority were collected in the straw and grass infusions. During week 6, the hay infusions had significantly more egg rafts when compared to manure (P<0.001) and rabbit infusions (P<0.001) and the grass infusions had significantly more when compared to manure (P<0.05) and rabbit (P<0.01). Week 9 also showed significance when the hay infusions collected significantly more egg rafts than manure and rabbit (P<0.01 and P<0.01, respectively). The attractiveness of the cow manure and straw infusions were also compared in gravid traps. Because it is difficult to accurately discriminate between Cx. pipiens and Cx. restuans that have been collected as adults in gravid traps, these collections were combined into Culex. More Culex mosquitoes were collected in the manure infusions for the first two weeks (P<0.05). No significant differences were found between the numbers of mosquitoes captured in the traps baited with the different infusions after the second week. The shift observed in oviposition preference for both types of traps may have been due to cooler temperatures in the early part of the season. The straw infusions were aged outdoors for 3 days prior to use, and a sufficient incubation temperature to generate the bacteria producing the attractant chemicals may not have been attained. In addition, the manure lagoon had been drawn down and the consistency of the remaining manure became much drier by this time. No chemicals were ever added to the lagoon, but the draw down may have affected the attractiveness of the manure. / Master of Science

Des modèles épidémiologiques capables de représenter des situations naturelles peuvent en principe permettre de caractériser et quantifier les risques d'épidémies ainsi que d'optimiser les moyens de les contrôler. On présente d'abord quelques modèles épidémiologiques d'usage courant et évalue leur capacité à représenter correctement une situation biologique. L'emphase est placée sur l'importance des délais ainsi que sur l'impact des conditions environnantes. On montre que des modèles basés sur l'équation de diffusion répondent particulièrement bien à ces critères et mènent à une formulation générale, directe et élégante. Sous certaines hypothèses, ces systèmes peuvent être partiellement solutionnés analytiquement, réduisant substantiellement les traitements numériques et permettant une meilleure compréhension de structures sous-jacentes. On compare ensuite certains de ces modèles dans le contexte particulier du virus du Nil Occidental et élabore une approche spécifique et réaliste afin de fournir des outils supplémentaires au processus décisionnel de prévention de cette maladie. / Epidemiological models capable of representing naturally occurring situations may in principle permit the characterization of the risks of epidemies as well as the optimization of means for controlling them. First, we present some typical epidemiological models currently in use and evaluate their ability to correctly describe a biological situation. Emphasis is placed on the possibility of the treatment of delays and on the inclusion of the effects of environmental conditions. We show that models based on a diffusion-type equation are particularly well suited to satisfy these conditions and lead to a general, direct and elegant formulation. Under not too restrictive hypotheses, the corresponding models can in part be treated analytically, reducing substantially the computational efforts, and allowing for a better understanding of the associated underlying structures. We then compare some of the models for the application to the West Nile virus and develop a specific and realistic approach to provide additional tools for the decision process in matters of prevention and propagation of the disease.