Abstract
Helminth infections are triggered by a variety of worm species and show a variety of symptoms which can lead to death. A large majority of helminth infections are considered as neglected tropical diseases which are associated with poverty receive little attention and very little research funding. Based on parasitological, serological, ophthalmological and entomological examinations it could be proven that transmission of Onchocerca volvulus in north and central Togo is still ongoing. Both, children and adults had antibodies against O. volvulus antigens. Eye pathologies suggesting an active infection with O. volvulus were also been found. The allover prevalence in the study areas was below 5%, but prevalences between 5% and 10% were found in some villages. Strong seasonal migration in and out of the endemic areas, especially into neighboring countries has left many people unaffected during mass treatment and may present a possible reservoir for the parasite. To reach elimination of onchocerciasis, it is necessary to include further activities beyond the treatment with ivermectin. Particular attention should be paid to the seasonal transnational migration of the population and to timely coordination of future ivermectin treatments with neighboring national onchocerciasis control programs. Mass treatment with ivermectin has drastically reduced the number of microfilariae in the skin and the "gold standard" is no longer sensitive enough to reliably detect infections with O. volvulus. For the first time, immunoprecipitation was used to isolate O. volvulus-specific peptides from antigen-presenting cells in onchocercomata tissues and then identify them by mass spectrometry. Peptides found were derived from the immunodominant Ov33 protein, P-glycoprotein, onchocystatin and Wolbachia, the endosymbiont of O. volvulus. Using epitope prediction and synthesis of overlapping Ov33 peptides, additional O. volvulus-specific peptides were identified. In IgG-specific ELISAs, peptides were recognized with a high sensitivity by onchocerciasis patients. Using a ROC analysis, 4 peptides were identified which showed a sensitivity of 100% and a specificity of over 80%. The combined use of those peptides could increase the sensitivity and specificity of serological tests. Another neglected disease is the alveolar echinococcosis. If left untreated, this worm can lead to death. Benzimidazoles, the only therapeutic drugs currently available, have only parasitostatic effects on the parasite. However, some patients show serious side effects on these medications. Analysis of Echinococcus multilocularis metacestoden cDNA on human microarrays showed strong expression of genes associated with cancer. Based on these findings, cytostatic FDA-approved anti-cancer drugs have been selected and tested both in vitro and in vivo. Parasite growth was inhibited by docetaxel, whereas paclitaxel and navelbine only slowed growth for up to 3 months. Vorinostat and doxorubicin had no detectable effects. The application of these drugs in other preclinical studies could help to develop new treatments for Echinococcus multilocularis infection.
Author and committee
dc:creator, dc:contributor.*- Author
-
- Voßberg, Patrick
Identifiers
dc:identifier.*- Identifier
- hdl:10900/93496