Studies on the pathogenesis and control of parasitic infections

Abstract

The work represented in this thesis covers three areas: the pathogenesis and immunobiology of nematode infections, the control and elimination of filarial nematode diseases, and lastly contributions to experimental and diagnostic pathology involving different diseases and medical conditions. A number of fundamental concepts are addressed: the role of eosinophil leucocytes in directly killing certain stages of helminths, acting in conjunction with antibodies and complement; the clinical significance of cell mediated immune responses in human onchocerciasis and its relationship to the clinical variation seen in this disease, including the classification of onchodermatitis in humans. The studies in chemotherapy focus not only understanding the pathological effects of chemotherapy in filariasis, but also on understanding the mechanisms of action of these anthelminthic drugs and the role of the host in their action; the function and action of two major anti-filarial agents, diethylcarbamazine and ivermectin, are now understood from this work. The more recent studies describe work towards developing more effective and safer anti-filarial drugs, with flubendazole being a major focus. A central theme of the research is translating laboratory work into field relevance in the diseases that cause significant morbidity in animals and humans, namely onchocerciasis, lymphatic filariasis, and canine dirofilariasis. The fieldwork presented also includes effects of the mass distribution of drugs used to eliminate the infection. A major success has been achieved with the progress towards elimination of onchocerciasis and filariasis from Ecuador, Sudan and Tanzania. Lastly, this collection of studies covers a range of areas that have been investigated by the author as part of serving as a general pathologist in academic setting contributing to equine medicine, wound healing, toxic disasters and breast cancer.