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Background: Despite the acknowledged importance of economic assessments for public health interventions at the human-animal-ecosystem interface, there are currently limited economic methodologies for doing so. In this thesis studies were undertaken to ascertain the economic impact of interventions to control trypanosomiasis and taeniasis/cysticercosis in south-east Uganda and northern Lao PDR respectively. Also, in Uganda studies were done to find out if demand of draft cattle would be an important economic driver for spreading trypanosomiasis due to inter-district trade. Method: In Uganda, a one year recall cross-sectional baseline survey and an 18 month longitudinal survey of 660 households was conducted; to determine the benefits and changes due to restricted application of deltamethrin insecticide to only the legs, belly and ears of cattle. During the 18 month study, the households participating in the study were divided into six regimes depending on the type of intervention done in their cattle and these were; diminazine injection only, deworming only, no treatment and those had 25%, 50% and 75% of the total village cattle sprayed. Thus, the first three regimes were those households that had their cattle not sprayed with insecticide at all as opposed to the last three. Additionally, cattle trade data was collected for network and value chain analysis in all markets in Tororo and Namutamba districts from 199 cattle traders. In northern Lao PDR, stochastic modelling was done to determine the burden of neurocysticercosis associated epilepsy and soil transmitted helminthes. A cross-sectional study was carried out in 49 households, focusing on the prevalence of cysticercosis and soil transmitted helminths before and after a twelve month intervention to control a hyperendemic focus of Taenia solium. The village data was then extrapolated to the wider northern Lao PDR population. Results: The Uganda study indicated that the restricted application of deltamethrin in cattle induced change of USD 31 per head of adult bovine per year; this was the change in income that directly occurred due to restricted spraying of cattle with deltamethrin. During the intervention period, the annual difference in income between those households that had their cattle sprayed using restricted application protocol and those that did not was USD 123; and this was significant (t= 7.18, p= < 0.001). Analysis of variance using households that had their cattle receive no treatment as control showed that restricted application of deltamethrin significantly increased household income compared to diminazine aceturate injection and deworming of cattle only. The incremental benefit cost ratio of spraying 0% to 25% of the cattle was found to be the highest (16:1) compared to spraying 25% to 50% (3:1) and 50% to 75% (1:1) of the cattle. Cattle trade network and value chain analysis revealed that the key cattle markets from which trypanosomiasis is likely to spread into Tororo District are Molo, Namutumba and Soroti. Also, it was found that the risk of spread of human African trypanosomiasis from south-east to north-west Uganda is high due to the increased demand for male cattle for draft work. In northern Lao PDR, 5,094 (95% CI: 25.6-28,940) DALYs were estimated to be imposed annually due to Taenia solium associated epilepsy, with 446.4 (95% CI: 2.2- 2,536) DALY imposed per 100,000 person-years. Due to the high benefits to pig production, the net monetary cost per DALY averted for simultaneously controlling T. solium, soil transmitted helminthes and classical swine fever was only USD 14, which fell to USD 11 if the separable cost method were applied. If the intervention did not target pigs, then the cost per DALY averted was USD 44; well below the current standard for ’very cost effective ‘of the 1 year’s per capita GDP. Conclusion: This study provided empirical evidence for evaluating the impact of quantifying the benefits of controlling zoonotic diseases in the livestock sector (Uganda case study) and in both livestock and human health populations (Lao PDR case study); this economic assessment approach can be used for planning future integrated health interventions. The results of this study support the policy of preventing the spread of infection by spraying at least 25% of the cattle using RAP, as well as injecting all cattle in key livestock markets in south east Uganda with diminazine aceturate to prevent HAT. In northern Lao PDR, simultaneous control of T. solium, soil transmitted helminths and classical swine fever is the most cost-effective approach. There are still difficulties in incorporating human and animal parameters into a single analytical framework; consequently there is a need to adapt the approaches undertaken in this study to the analysis of other zoonotic diseases in different settings to improve on their robustness.

Computer-aided drug discovery involves the application of computer science and programming to solve chemical and biological problems. Specifically, the QSAR (Quantitative Structure Activity Relationships) methodology is used in drug development to provide a rational basis of drug synthesis, rather than a trial and error approach. Molecular dynamics (MD) studies focus on investigating the details of drug-target interactions to elucidate various biophysical characteristics of interest. Infectious diseases like Trypanosoma brucei rhodesiense (TBR) and P. falciparum (malaria) are responsible for millions of deaths annually around the globe. This necessitates an immediate need to design and develop new drugs that efficiently battle these diseases. As a part of the initiatives to improve drug efficacy QSAR studies accomplished the formulation of chemical hypothesis to assist development of drugs against TBR. Results show that CoMSIA 3D QSAR models, with a Pearson’s correlation coefficient of 0.95, predict a compound with meta nitrogens on the phenyl groups, in the combinatorial space based on a biphenyl-furan diamidine design template, to have higher activity against TBR relative to the existing compound set within the same space. Molecular dynamics study, conducted on a linear benzimidazole-biphenyl diamidine that has non-classical structural similarity to earlier known paradigms of minor groove binders, gave insights into the unique water mediated interactions between the DNA minor groove and this ligand. Earlier experiments suggested the interfacial water molecules near the terminal ends of the ligand to be responsible for the exceptianlly high binding constant of the ligand. Results from MD studies show two other modes of binding. The first conformation has a single water molecule with a residency time of 6ns (average) that is closer to the central part of the ligand, which stabilizes the structure in addition to the terminal water. The second conformation that was detected had the ligand completely away from the floor of the minor groove, and hydrogen bonded to the sugar oxygens.

A class of linear diamidines was synthesized for the evaluation as a treatment of Human African Trypanosomiasis. These fused heterocyclic compounds are thiazole[5,4-d]thiazoles and are of interest because the parent compound, 2,5-Bis(4-amidinophenyl)-thiazolo[5,4-d]thiazole HCl salt, which is also called DB 1929, has exhibited a low nanomolar IC50 value against Trypanosoma brucei rhodesiense and has shown selectivity for binding to the human telomere G-quadruplex over that of DNA duplex. A fluoro and a methoxy derivative have been synthesized and are currently undergoing testing for activity and binding affinity. In addition, fluorescence studies of selected diamidines were done to study the effect of structural variation on fluorescence. This data is useful since it can determine what types of moieties are needed to yield a compound that will fluoresce in the higher wavelengths (500 nm and above) of the visible spectrum, which would be advantageous in determining the uptake of the drug in the trypanosome within the endemic areas of Africa with a simple microscope.