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Content archived on 2024-04-19

Ivermectin facilitated immunity onchocerciasis

Objective



The host immune response to filarial parasites is a critical determinant of manifestation of disease and of disease severity. In the treatment of onchocerciasis a single dose of ivermectin activates the suppressed immune response of patients, but the immnological mechanisms effective during the elimination of microfilariae and their contribution to long lasting control of disease, are not well understood. Therefore, the objectives of the proposal are:
1. To activate the parasite-specific immune response in onchocerciasis patients after single and repeated doses of ivermectin. At present, our observations have shown a partial activation of the immune response after single dose treatment. Repeated doses and longitudinal examination of the immune response will delineate those factors and those mechanisms which are involved to constantly suppress microfilaridermia. 2. To characterize and to localize immunodominant O.volvulus antigens, potentially involved in protection and/or pathogenesis. An activation of the suppressed immune response in onchoerciasis patients by chemotherapy will identify those antigens which are immunodominant during the active immune response. Such antigens are of potential value for the development of a vaccine, but will also be examined for their potential to induce exacerbation of disease.
3. To analyse the functional potential of immunogenic O.volvulus antigens. Longitudinal examination of cellular reactivity against O.volvulus derived antigens concurrent with the measurement of cytokine production will delineate the importance and effects of cytokines during immunological hypo- and hyperreactivity in patients. Successive analysis of cells activated by filarial antigens will characterize those cells that contribute to the elimination of microfilariae.
4. To examine a possible immunodependant regulation of the reproductivity of O.volvulus. The observed clearance of skin microfilariae in ivermectin treated patients can be explained either by an activation of the most immune response, or alternatively by a reduced microfilarial release from gravid adult female worms, or by a disturbed intra-uterine development of microfilariae. All three mechanisms could be induced by drug facilitated immunity.

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Funding Scheme

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Coordinator

THE UNIVERSITY OF TUEBINGEN
EU contribution
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Address
27,Wilhelmstrasse 27
72074 TUEBINGEN
Germany

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Total cost

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Participants (2)

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