Investigating novel approaches to the detection of virus neutralising antibodies to rabies and Rift Valley fever virus

Serosurveillance is a powerful tool fundamental to understanding infectious disease dynamics. The presence of virus neutralising antibody (VNAb) in sera is considered the best evidence of infection, or indeed vaccination, and the gold standard serological assay for their detection is the virus neutralisation test (VNT). However, VNTs are labour intensive, costly and time consuming. In addition, VNTs for the detection of antibodies to highly pathogenic viruses require the use of high containment facilities, restricting the application of these assays to the few laboratories with adequate facilities. As a result, robust serological data on such viruses are limited. In this thesis I develop novel VNTs for the detection of VNAb to two important, highly pathogenic, zoonotic viruses; rabies and Rift Valley fever virus (RVFV). The pseudotype-based neutralisation test developed in this study allows for the detection of rabies VNAb without the requirement for high containment facilities. This assay was utilised to investigate the presence of rabies VNAb in animals from a variety of ecological settings. In this thesis I present evidence of natural rabies infection in both domestic dogs and lions from rabies endemic settings. The assay was further used to investigate the kinetics of VNAb response to rabies vaccination in a cohort of free-roaming dogs. The RVFV neutralisation assay developed herein utilises a recombinant luciferase expressing RVFV, which allows for rapid, high-throughput serosurveillance of this important neglected pathogen. In this thesis I present evidence of RVFV infection in a variety of domestic and wildlife species from Northern Tanzania, in addition to the detection of low-level transmission of RVFV during interepidemic periods. Additionally, the investigation of a longitudinal cohort of domestic livestock also provided evidence of rapid waning of RVF VNAb following natural infection. Collectively, the serological data presented in this thesis are consistent with existing data in the literature generated using the gold standard VNTs. Increasing the availability of serological assays will allow the generation of robust serological data, which are imperative to enhancing our understanding of the complex, multi-host ecology of these two viruses.

Geological Characterisation of Depleted Oil and Gas Reservoirs for Carbon Sequestration Potentials in a Field in the Niger Delta, Nigeria

The injectivity, containment and storage capacity of sandstone reservoirs in a field in the Coastal Swamp depobelt of the onshore eastern Niger Delta were evaluated using wireline logs and seismic data to assess their potentials for carbon dioxide storage and geosequestration. The reservoir formation consists of multilayered alternating beds of sandstone and shale cap rocks. Active seismicity and fracturing intensity are low and growth faults provide the reservoir sealing mechanisms. Three reservoirs were delineated at depths between 3319 m and 3539 m which will keep injected CO2 in a supercritical state. The reservoir depth of at least 800 m, porosity and permeability of more than 10 percent and 20 mD, and a caprock thickness of at least 10 m, in addition to geothermal gradients of 13.46 to 33.66 ºC /km are the ideal conditions for the efficacy of storage. Comparison of the derived reservoir and seal properties such as porosity, permeability, thickness and depth with the minimum recommended site selection criteria shows that the reservoirs are potential candidates for carbon geosequestration with a total theoretical storage capacity of 147MM tons.

Frequency and molecular characterisation of Entamoeba histolytica , Entamoeba dispar , Entamoeba moshkovskii , and Entamoeba hartmanni in the context of water scarcity in northeastern Brazil

This study aimed to estimate the frequency, associated factors, and molecular characterisation of Entamoeba histolytica , Entamoeba dispar, Entamoeba moshkovskii , and Entamoeba hartmanni infections. We performed a survey (n = 213 subjects) to obtain parasitological, sanitation, and sociodemographic data. Faecal samples were processed through flotation and centrifugation methods. E. histolytica, E. dispar, E. moshkovskii, and E. hartmanni were identified by nested-polymerase chain reaction (PCR). The overall prevalence of infection was 22/213 (10.3%). The infection rate among subjects who drink rainwater collected from roofs in tanks was higher than the rate in subjects who drink desalinated water pumped from wells; similarly, the infection rate among subjects who practice open defecation was significantly higher than that of subjects with latrines. Out of the 22 samples positive for morphologically indistinguishable Entamoeba species, the differentiation by PCR was successful for 21. The species distribution was as follows: 57.1% to E. dispar, 23.8% to E. histolytica, 14.3% to E. histolytica and E. dispar, and 4.8% E. dispar and E. hartmanni. These data suggest a high prevalence of asymptomatic infection by the group of morphologically indistinguishable Entamoeba histolytica/dispar/moshkovskii complex and E. hartmanni species. In this context of water scarcity, the sanitary and socioenvironmental characteristics of the region appear to favour transmission.

WATER RESOURCES, HEALTH, AND THE SUSTAINABILITY OF INTERVENTIONS TO ACHIEVE WATER AND SANITATION TARGETS OF THE MILLENNIUM DEVELOPMENT GOALS IN A CHANGING WORLD

This dissertation addresses sustainability of rapid provision of safe water and sanitation required to meet the Millennium Development Goals. Review of health-related literature and global statistics demonstrates engineers' role in achieving the MDGs. This review is followed by analyses relating to social, environmental, and health aspects of meeting MDG targets. Analysis of national indicators showed that inadequate investment, poor or nonexistent policies and governance are challenges to global sanitation coverage in addition to lack of financial resources and gender disparity. Although water availability was not found to be a challenge globally, geospatial analysis demonstrated that water availability is a potentially significant barrier for up to 46 million people living in urban areas and relying on already degraded water resources for environmental income. A daily water balance model incorporating the National Resources Conservation Services curve number method in Bolivian watersheds showed that local water stress is linked to climate change because of reduced recharge. Agricultural expansion in the region slightly exacerbates recharge reductions. Although runoff changes will range from -17% to 14%, recharge rates will decrease under all climate scenarios evaluated (-14% to -27%). Increasing sewer coverage may place stress on the readily accessible natural springs, but increased demand can be sustained if other sources of water supply are developed. This analysis provides a method for hydrological analysis in data scarce regions. Data required for the model were either obtained from publicly available data products or by conducting field work using low-cost methods feasible for local participants. Lastly, a methodology was developed to evaluate public health impacts of increased household water access resulting from domestic rainwater harvesting, incorporating knowledge of water requirements of sanitation and hygiene technologies. In 37 West African cities, domestic rainwater harvesting has the potential to reduce diarrheal disease burden by 9%, if implemented alone with 400 L storage. If implemented in conjunction with point of use treatment, this reduction could increase to 16%. The methodology will contribute to cost-effectiveness evaluations of interventions as well as evaluations of potential disease burden resulting from reduced water supply, such as reductions observed in the Bolivian communities.

The Development of Calibrants through Characterization of Volatile Organic Compounds from Peroxide Based Explosives and a Non-target Chemical Calibration Compound

Detection canines represent the fastest and most versatile means of illicit material detection. This research endeavor in its most simplistic form is the improvement of detection canines through training, training aids, and calibration. This study focuses on developing a universal calibration compound for which all detection canines, regardless of detection substance, can be tested daily to ensure that they are working with acceptable parameters. Surrogate continuation aids (SCAs) were developed for peroxide based explosives along with the validation of the SCAs already developed within the International Forensic Research Institute (IFRI) prototype surrogate explosives kit. Storage parameters of the SCAs were evaluated to give recommendations to the detection canine community on the best possible training aid storage solution that minimizes the likelihood of contamination. Two commonly used and accepted detection canine imprinting methods were also evaluated for the speed in which the canine is trained and their reliability. As a result of the completion of this study, SCAs have been developed for explosive detection canine use covering: peroxide based explosives, TNT based explosives, nitroglycerin based explosives, tagged explosives, plasticized explosives, and smokeless powders. Through the use of these surrogate continuation aids a more uniform and reliable system of training can be implemented in the field than is currently used today. By examining the storage parameters of the SCAs, an ideal storage system has been developed using three levels of containment for the reduction of possible contamination. The developed calibration compound will ease the growing concerns over the legality and reliability of detection canine use by detailing the daily working parameters of the canine, allowing for Daubert rules of evidence admissibility to be applied. Through canine field testing, it has been shown that the IFRI SCAs outperform other commercially available training aids on the market. Additionally, of the imprinting methods tested, no difference was found in the speed in which the canines are trained or their reliability to detect illicit materials. Therefore, if the recommendations discovered in this study are followed, the detection canine community will greatly benefit through the use of scientifically validated training techniques and training aids.