No description available.

Dedicated to Dr. William A. Todd, of Downingtown, Pa. / Last page blank.

Dedicated to Dr. William A. Todd, of Downingtown, Pa. / Last page blank. Microform version available in the Readex Early American Imprints series.

Aquatic pollution from urban and industrial effluents represents a growing area of concern. The number and volume of xenobiotic chemicals in aquatic ecosystems is alarmingly high, due in part to increasing globalization and the associated demands. Invertebrates, in particular molluscs, represent species of great commercial importance and can therefore fail to be considered in terms of their significance in the transmission of human disease. Schistosoma mansoni is a trematode parasite transmitted to humans by aquatic snails of the genus Biomphalaria. S.mansoni infects up to 200 million people globally and transmission primarily occurs in developing countries with poor infrastructure, factors which also happen to be associated with high levels of aquatic pollution. Despite the medical importance of S.mansoni and its occurrence in potentially polluted environments, very few attempts have been made to study this parasite-host relationship in the context of ecotoxicology. In this thesis I have applied both adapted and novel approaches in order to combine the fields of parasitology and ecotoxicology toward a better understanding of the effects of globally-prevalent xenobiotic chemicals on the S.mansoni-B.glabrata relationship. In vitro assays, with various end-points, were performed based on exposure of hemocytes, the primary immune effector cells of molluscs, while whole snails were developmentally exposed to an effluent extract and subsequently infected as part of an in vivo study. Taken together, my results suggest that the immunocompetance of B.glabrata hemocytes is broadly reduced in the presence of DDE, BPA, E2 and an effluent extract; chemicals that occur at high levels in transmission countries. Reduction in the key hemocyte functions of motility, phagocytosis and encapsulation, caused by exposure to these chemicals, appears to be exacerbated by subsequent S.mansoni infection which results in an opportunity for increased parasite shedding. My hope is that this broad work will serve as a reference and facilitate more focused studies, particularly of a molecular and epidemiological nature, into what is an understudied and potentially very important topic with the potential for human health implications.

O'nyong-nyong virus (ONNV) is an Alphavirus (family: Togaviridae) transmitted by Anopheles gambiae (An. gambiae) mosquitoes. Alphavirus transmission causes a number of severe diseases in vertebrates. However, in mosquito hosts, infection rarely causes pathology. To date, little is known about the cellular responses that privilege mosquitoes with the ability to cope with infection. This study evaluated the genetic responses of An. gambiae to ONNV infection. We adopted a proteomics approach to identify proteins and molecular pathways that respond to virus infection in the midgut, the primary physical and biological barrier to infection. The sensitive mass spec-based technique, Tandem Mass Tagging (TMT; Thermo Scientific), was used to quantify and compare protein expression changes induced by the virus. Several proteins were identified that mediated virus infection, including an FK506 binding protein (FKBP). Evidence suggests FKBPs are phylogenetically conserved virus resistance factors that may exert their function via the PI3K/Akt/TOR pathway. There are many powerful tools for investigating protein function, such as reverse genetics using RNA interference (RNAi). This technique, however, requires the ability to consistently and efficiently transfect cells, which has proven difficult with regard to mosquito studies; there is currently no acceptable in vitro model for studying gene function in An. gambiae. Therefore, having identified proteins of importance to virus infection, we next created an in vitro model system for future protein function studies. By evaluating different transfection reagents and cell culture methods, we developed a method for transfecting the immune-competent Sua5b (An. gambiae) cell line with very high efficiency. Finally, we evaluated the role of the PI3K/Akt/TOR pathway in o'nyong-nyong virus infection of both mammalian (Vero) and mosquito (Sua5b) cells. This pathway offered a window of understanding into how alphaviruses interact with their hosts, and perhaps more importantly, in what ways those interactions differ. We found that the PI3K/Akt/TOR pathway likely plays distinct, if not opposite roles in infection of the host cells studied. / acase@tulane.edu

This thesis deconstructs the social, ecological, and colonial elements of the 1900-1910 Human African Trypanosomiasis (African Sleeping Sickness) epidemic which affected British Uganda and Belgian Congo. This paper investigates the epidemic’s medical history, and the subsequent social control policies which sought to govern the actions of the indigenous population. In addition, this paper argues that the failure to understand and respect the region’s ecological conditions and local knowledge led to disease outbreaks in epidemic proportions. Retroactive policies sought to inflict western medical practices on a non-western population, which resulted in conflict and unrest in the region. In the Belgian Congo, colonial authorities created a police state in which violence and stringent control measures were used to manage the local population. In Uganda, forced depopulation in infected regions destabilized local economies. This thesis compares and contrasts the methods used in these regions, and investigates the effects of Germ Theory on Sleeping Sickness policy and social perceptions during the colonial period in Africa.

acase@tulane.edu

acase@tulane.edu

acase@tulane.edu

acase@tulane.edu