Flaviviruses are a single-stranded, positive sense, RNA virus that affect around 400 million people annually. Flaviviruses are transmitted by arthropod vectors, the most common vector being the mosquito. Currently, many mosquito control strategies are in use, these control strategies are diverse in both efficiency and cost. However, developing new vector control strategies is becoming increasingly important, due to climate changing affecting vector population distribution and the current limitations conventional control strategies face. Although many different control strategies exist, there is limited research pertaining to reducing viral infection in the vector. Reducing the transmission capabilities of vectors could help relieve the disease burden felt around the world. Aripo virus (ARPV), an insect-specific flavivirus, has ushered in opportunities to discover a novel approach to arbovirus control. The exclusionary effects of ARPV were explored as a means to eventually understanding superinfection exclusion (SIE) and utilizing it as a calculated defense against mosquito-borne disease. Aripo virus was evaluated for its SIE potential in vitro and experiments were performed to explore the possible mechanisms underlying SIE. Aripo virus showed significant exclusion against the flaviviruses tested, as well as an alphavirus. Additionally, West Nile virus was unable to adapt and overcome SIE barriers over 9 serial passages. Lastly, ARPV was superinfected with chimeric viruses to asses replication kinetics, and possible exclusionary bias was seen with non-structural genes. These data show ARPV is capable of reducing viral titer, as well as possible leads into understanding the underlying mechanism of SIE, a critical step in utilizing SIE as a strategy to combat vector-borne disease. / Master of Science in Life Sciences / Mosquitoes all around the globe spread disease causing pathogens. Infection with viral pathogens such as West Nile virus, Zika virus, and Japanese encephalitis virus can cause lifelong health effects or even death. Risk for increased spread of mosquito-vectored disease is on the rise. The continued effects of climate change, increasing temperatures away from the equator, and increased encroachment into natural areas for urban development, is opening the door for new infectious diseases spread by mosquitoes. There are many ways to curb the effects that these viral diseases can have on humans, including vaccines or mosquito repellents, and even eliminating mosquito populations is helping to reduce the effects of these important diseases. Sadly, no one method can solve the problem. The methods of dealing with mosquito transmitted disease are likely to be most effective when done in combination. The more countermeasures that attempt to stop the spread of disease, the greater dent in reducing the spread of disease. In this dissertation, we dive into the realm of stopping disease transmission before humans become a factor. If we can limit mosquito infections, then the disease has no way of reaching humans. An approach to controlling mosquito infections could lie within viruses themselves. Aripo virus, an insect-specific virus, is interesting in that it does not affect vertebrates, only mosquitoes. When Aripo virus infects mosquito cells at the same time as deadly viruses, the deadly viruses do not accumulate in the mosquito cells nearly as much. Within mosquito cells, Aripo virus was able to reduce the levels of West Nile virus, St. Louis encephalitis virus, Japanese encephalitis virus, Zika virus, and Mayaro virus. If the underlying concept of the method of Aripo virus induced exclusion of deadly viruses could be further understood, it could be used to reduce the spread of mosquito-related viral diseases.

Ross River virus (RRV) is an Alphavirus distributed throughout Australia. It is transmitted by mosquitoes and is known to cause moderate to severe disease symptoms in humans. Along with other alphaviruses such as Sindbis virus and Chikungunya virus, RRV is known to cause arthritic symptoms, characterised by muscle and joint inflammation. Several investigations have established the role of macrophage cells and pro-inflammatory host factors in the development of RRV-induced disease. In this study, we attempted to determine differences between RRV passaged in mammalian and mosquito cells. There is strong evidence that arthropod-borne viruses are able to display enhanced infectivity when passaged into arthropod cell line. We showed that mosquito cell-derived RRV (mos-RRV) was able to replicate to higher titres than mammalian cell-derived RRV. We also showed that mos-RRV failed to induce Type I IFN-associated antiviral responses. The second aim of this study was to investigate the role of TNF-ᬠa pro-inflammatory cytokine implicated in arthritic diseases, in the development of RRV disease. We treated RRV-infected C57BL/6J mice with a commercially available TNF-ᠩnhibitor drug and monitored disease signs. We found that the TNF-ᠩnhibitor does not ameliorate RRV disease (RRVD) symptoms, and that it does not prevent muscle and joint inflammation. We analysed histological sections of muscle and joint tissue of Enbrel-treated and untreated, RRV-infected cells. We also determined and compared host cytokine expression profiles. Finally, we sought to determine the requirement for natural killer (NK) cells in RRV disease. NK cells have been detected in the synovium of RRV-infected patients since early studies, but their role in disease pathogenesis remains unclear. Using a NK-dysfunctional mouse (C57BL/6J-Lystbg), we showed that mice lacking a functional NK system are more susceptible to RRV disease than wildtype, C57BL/6J mice. We monitored disease symptoms following RRV infection and assessed muscle and joint inflammation in Lystbg and C57BL/6J mice. This thesis examines mechanisms of viral infection and immune evasion employed by RRV, as well as into the role of host cells and cytokines in RRVD pathogenesis disease mechanisms. We showed that a functional NK cell system is required for the regulation of RRV-induced muscle and joint inflammation. Our characterisation of the use of a commercial TNF-ᠩnhibitor in RRV-induced disease in mice may provide information on the role of TNF-ᠩn viral arthritis, and may help towards developing safe and effective treatment.

The intent of this thesis is to develop ordinary differential equation models to better understand the mosquito population. We first develop a framework model, where we determine the condition under which a natural mosquito population can persist in the environment. Wolbachia is a bacterium which limits the replication of viruses inside the mosquito which it infects. As a result, infecting a mosquito population with Wolbachia can decrease the transmission of viral mosquito-borne diseases, such as dengue. We develop another ODE model to investigate the invasion of Wolbachia in a mosquito population. In a biologically feasible situation, we determine three coexisting equilibria: a stable Wolbachia-free equilibrium, an unstable coexistence equilibrium, and a complete invasion equilibrium. We establish the conditions under which a population of Wolbachia infected mosquitoes may persist in the environment via the next generation number and determine when a natural mosquito population may experience a complete invasion of Wolbachia.

No description available.

Virginia's temperate climate is suitable for several mosquito species capable of transmitting pathogens to humans. In southwest Virginia, La Crosse encephalitis and West Nile fever are most prominent. The objective of this research, which uses the Health Belief Model (HBM) as a theoretical framework, is to assess knowledge of mosquito-borne disease in southwest Virginia, as well as perceptions and practices of mosquito prevention. Given that several cases of La Crosse encephalitis have been reported in Wise and Tazewell counties, they were selected as study sites to conduct surveys. Five demographic and socioeconomic variables (gender, age, income, education level and length of time one has lived in the county) were used as predictor variables in logistic regression analyses. Gender, age, and length of residence time in the county were found to be statistically significant predictors of specific health-related behaviors. Within the framework of the HBM, barriers to removing standing water around the home and wearing insect repellent were highlighted. Knowledge of mosquito-borne diseases within the area was generally low, with only one individual correctly identifying La Crosse encephalitis as a threat in the region. Higher numbers (6%) were aware of West Nile virus, while 4% reported malaria in the region, demonstrating a disconnect between actual and perceived risk. These results can enhance existing public health programs by increasing knowledge, addressing public uncertainty about insect repellent safety, and addressing ways to make recommended practices more effective with the knowledge of how different aspects are perceived by varying groups within the community. / Master of Science

The global incidence of dengue has increase 30-fold over the past 50 years in the western or Asian Pacific, this region is also a contemporary epicenter for resource extraction and ecological destabilization. Dengue is addition to yellow fever, chikungunya and most recently zika virus, are transmitted by the mosquito vector Aedes aegypti- a domesticated mosquito adept at breeding in artificial household containers and within homes. The history of the domestication and global distribution of Aedes aegypti is intrinsically linked to European expansion into and among tropical worlds. Contemporary population genetics research suggest the westward expansion of the mosquito vector beginning with trans-Atlantic Slave Trade moving to the Americas and then making a jump across the Pacific, which I argue occurred first within the Philippines and then spread eastward through the greater Indian Ocean. I argue that Spanish and American colonization facilitated the biological invasion of Ae. aegypti and dengue in the Philippines and created the conditions for contemporary epidemics. The discourse within the dominant voices of public health, CDC and WHO, omit this history as well as down play the significance of land use and deforestation while focusing predominantly upon dengue’s prevention and control. This omission is an act of erasure and a means of furthering western imperialism through paternalistic interventions. Mosquito-borne disease epidemics are unintended consequences of past human action and if public health discourse continues to frame epidemics as random and unfortunate events, we risk missing key patterns and continuing to perpetuate the circumstances of disease and adaptation.

abstract: Despite the arid climate of Maricopa County, Arizona, vector-borne diseases have presented significant health challenges to the residents and public health professionals of Maricopa County in the past, and will continue to do so in the foreseeable future. Currently, West Nile virus is the only mosquitoes-transmitted disease actively, and natively, transmitted throughout the state of Arizona. In an effort to gain a more complete understanding of the transmission dynamics of West Nile virus this thesis examines human, vector, and environment interactions as they exist within Maricopa County. Through ethnographic and geographic information systems research methods this thesis identifies 1) the individual factors that influence residents' knowledge and behaviors regarding mosquitoes, 2) the individual and regional factors that influence residents' knowledge of mosquito ecology and the spatial distribution of local mosquito populations, and 3) the environmental, demographic, and socioeconomic factors that influence mosquito abundance within Maricopa County. By identifying the factors that influence human-vector and vector-environment interactions, the results of this thesis may influence current and future educational and mosquito control efforts throughout Maricopa County. / Dissertation/Thesis / M.S. Sustainability 2013

[Truncated abstract] Ross River virus (RRV) causes the most common arboviral disease in Australia, with approximately 5000 new cases reported each year, making this virus a major public health concern. The aim of this thesis was to link results from virological, pathogenesis and epidemiological studies to further define RRV disease in the south-west (SW) of Western Australia (WA), a region of endemic and epizootic RRV activity. A crosssectional seroprevalence study was used to show that 7.8 percent of SW communities were seropositive to RRV, comparable to other regions of Australia with similar temperate climates to the SW . . . RRV-specific IgM antibodies were found to persist for at least two years following RRV infection. A murine model was used to conclusively show differences in pathogenesis between RRV genotypes, the SW and northern-eastern (NE) genotypes, which are known to circulate throughout Australia. The SW genotype, unique to the SW of WA induced only poor neutralising antibody production and nonneutralising antibodies after the acute phase of infection. In comparison, the NE genotype which currently predominates in mosquito populations in the SW of WA, induced the most efficient neutralising antibody response and consequently produced the mildest disease in the mouse. These data in the mouse suggest that the infecting genotype will mostly likely influence disease outcome in humans and could at least partially explain why more severe and persistent disease has been reported from the SW of WA. Collectively, results from this thesis provide an important benchmark against which future investigations into BFV and RRV diseases can be measured.

[Truncated abstract] A functional ecosystem is increasingly being recognised as a requirement for health and well being of resident human populations. Clearing of native vegetation for agriculture has left 1.047 million hectares of south-west Western Australia affected by a severe form of environmental degradation, dryland salinity, characterised by secondary soil salinisation and waterlogging. This area may expand by a further 1.7-3.4 million hectares if current trends continue. Ecosystems in saline affected regions display many of the classic characteristics of Ecosystem Distress Syndrome (EDS). One outcome of EDS that has not yet been investigated in relation to dryland salinity is adverse human health implications. This thesis focuses on one such potential adverse health outcome: increased incidence of Ross River virus (RRV), the most common mosquito-borne disease in Australia. Spatial analysis of RRV notifications did not reveal a significant association with dryland salinity. To overcome inherent limitations with notification data, serological RRV antibody prevalence was also investigated, and again no significant association with dryland salinity was detected. However, the spatial scale imposed limited the sensitivity of both studies. ... This thesis represents the first attempt to prospectively investigate the influence of secondary soil salinity on mosquito-borne disease by combining entomological, environmental and epidemiological data. The evidence collected indicates that RRV disease incidence is not currently a significant population health priority in areas affected by dryland salinity despite the dominant presence of Ae. camptorhynchus. Potential limiting factors include; local climatic impact on the seasonal mosquito population dynamics; vertebrate host distribution and feeding behaviour of Ae. camptorhynchus; and the scarce and uneven human population distribution across the region. However, the potential for increased disease risk in dryland salinity affected areas to become apparent in the future cannot be discounted, particularly in light of the increasing extent predicted to develop over coming decades before any benefits of amelioration strategies are observed. Finally, it is important to note that both dryland salinity and salinity induced by irrigation are important forms of environmental degradation in arid and semi-arid worldwide, with a total population of over 400 million people. Potential health risks will of course vary widely across different regions depending on a range of factors specific to the local region and the complex interactions between them. It is therefore not possible to make broad generalisations. The need is highlighted for similar research in other regions and it is contended that an ecosystem health framework provides the necessary basis for such investigations.