Onchocerciasis affects 50 million people causing up to 1 million cases of blindness, several million cases of severe visual impairment and, in many more, considerable pathological changes in the skin. The microfilariae (1st stage larvae) are responsible for this pathology. Immunity to mf in man varies considerably with intensity and duration of infections. In many patients, a large proportion of the mf is able to avoid the host immune mechanisms. One avoidance mechanism which may be important, and which has been shown to work to the parasites' advantage in infections with Trichinella spiralis, is the enzymatic degradation of free radicals generated by phagocytes/granulocytes. This study will look at the presence of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) principally in mf but also in adult worms and third stage larvae (L3s) of Onchocerca cervicalis, a common equine parasite in the USA which is very closely related to O. volvulus of man. Considerable dermal and ocular pathology also occurs in equines infected with this parasite.
The specific aims of this project are: 1. To identify by bioactivity, SOD, catalase and GSH-Px and to quantify the levels of these enzymes in mf, adult worms and L3s of O. cervicalis. 2. To purify and characterise these parasite radical scavenging enzymes and demonstrate identity from host enzymes. 3. To raise anti-worm SOD, catalase and GSH-Px antisera. 4. To determine the localization of these enzymes in the parasite and in vivo in host (horse and mouse) pathological lesions. 5. To determine the levels of scavenging enzymes in the excretory and secretory (E&S) products of mf (and L3s). 6. To determine the sensitivity in vitro of mf to toxic oxygen species and the importance of radical scavenging systems to the parasite. 7. To evaluate in vitro the ability of enzyme inhibitors and anti-enzyme antisera to enhance host effector cell adherence and killing. 8. To assess the ability of parasite radical scavenging enzymes to induce resistance to mf in vivo in mice. The long-term objective of this study is to determine the feasibility and likely effectiveness of a putative therapeutic/transmission-blocking vaccine which employs worm oxygen radical scavenging enzymes as antigens.
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