Immune recognition of excretory and secretory products of the filarial nematode Onchocerca ochengi in cattle and human sera.

Excretory-secretory (ES) products of nematodes and other helminths are the first molecules to interact with cell surfaces and soluble proteins within the host. In the present study, ES products of the filarial nematode Onchocerca ochengi were investigated as a model for Onchocerca volvulus, the causative agent of river blindness. These products were collected from adult and larval stages in vitro over a period of 7 days, to compare their immunological recognition in cattle and human sera, infected with species of Onchocerca. From the 156 sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) ES products or extracts, protein bands showed different patterns between female and male products. A comparison of antibody recognition of the different ES products by sera from infected cattle and humans, when analysed by enzyme-linked immunosorbent assay (ELISA), revealed a relatively higher reactivity of the female somatic extract to human and cattle sera compared to ES products of both genders. Nevertheless, similar reactivity of the O. ochengi male and female ES products to human and cattle sera was noticed. As a result, the interaction of ES products with the surface of the host and immune system often led to host responses, including the generation of antibodies. The O. ochengi ES products are therefore good sources of potential immunogenic proteins. The identification of these ES products is in progress, with the aim of developing vaccine candidates against human onchocerciasis.

Immune recognition of Onchocerca volvulus proteins in the human host and animal models of onchocerciasis.

Onchocerca volvulus is a tissue-dwelling, vector-borne nematode parasite of humans and is the causative agent of onchocerciasis or river blindness. Natural infections of BALB/c mice with Litomosoides sigmodontis and of cattle with Onchocerca ochengi were used as models to study the immune responses to O. volvulus-derived recombinant proteins (OvALT-2, OvNLT-1, Ov103 and Ov7). The humoral immune response of O. volvulus-infected humans against OvALT-2, OvNLT-1 and Ov7 revealed pronounced immunoglobulin G (IgG) titres which were, however, significantly lower than against the lysate of O. volvulus adult female worms. Sera derived from patients displaying the hyperreactive form of onchocerciasis showed a uniform trend of higher IgG reactivity both to the single proteins and the O. volvulus lysate. Sera derived from L. sigmodontis-infected mice and from calves exposed to O. ochengi transmission in a hyperendemic area also contained IgM and IgG1 specific for O. volvulus-derived recombinant proteins. These results strongly suggest that L. sigmodontis-specific and O. ochengi-specific immunoglobulins elicited during natural infection of mice and cattle cross-reacted with O. volvulus-derived recombinant antigens. Monitoring O. ochengi-infected calves over a 26-month period, provided a comprehensive kinetic of the humoral response to infection that was strictly correlated with parasite load and occurrence of microfilariae.

Anthelmintic activity of phenolic acids from the axlewood tree Anogeissus leiocarpus on the filarial nematode Onchocerca ochengi and drug-resistant strains of the free-living nematode Caenorhabditis elegans.

The effect of three phenols (ellagic, gentisic and gallic acids) from the axlewood tree Anogeissus leiocarpus on Onchocerca ochengi and drug-resistant strains of Caenorhabditis elegans, a model organism for research on nematode parasites, is investigated. Worms were incubated in different concentrations of phenols and their survival was monitored after 48 h. Among the three acids, ellagic acid strongly affected the survival of O. ochengi microfilariae, O. ochengi adults, a wild-type C. elegans and anthelmintic-resistant strains of C. elegans, namely albendazole (CB3474), levamisole (CB211, ZZ16) and ivermectin (VC722, DA1316), with LC50 values ranging from 0.03 mm to 0.96 mm. These results indicate that the binding of ellagic acid in the worm differs from that of resistant strains of C. elegans. The efficacy of both gallic and gentisic acids was not significantly changed in resistant strains of C. elegans treated with levamisole (ZZ16, LC50= 9.98 mm, with gallic acid), albendazole (CB3474, LC50= 7.81 mm, with gentisic acid) and ivermectin (DA1316, LC50= 10.62 mm, with gentisic acid). The efficacy of these three pure compounds is in accordance with the use of A. leiocarpus from its locality of origin. The in vivo toxicity data reveal that the thresholds are up to 200 times higher than the determined LC50 values. Thus, ellagic acid could be a potential option for the treatment of nematode infections, even in cases of drug resistance towards established anthelmintic drugs.

In vitro activity of Cameroonian and Ghanaian medicinal plants on parasitic (Onchocerca ochengi) and free-living (Caenorhabditis elegans) nematodes.

Ethanolic and aqueous extracts of selected medicinal plants from Cameroon and Ghana were assessed for their in vitro anthelmintic activity by using the bovine filarial parasite Onchocerca ochengi and the free living nematode Caenorhabditis elegans, a model organism for research on nematode parasites. Worms were incubated in the presence of different concentrations of extracts and inhibitory effects were monitored at different time points. Among the extracts used in this study, ethanolic extracts of Anogeissus leiocarpus, Khaya senegalensis, Euphorbia hirta and aqueous extracts from Annona senegalensis and Parquetina nigrescens affected the growth and survival of C. elegans and O. ochengi significantly. The mortality was concentration dependent with an LC50 ranging between 0.38 and 4.00 mg/ml for C. elegans (after 72 h) and between 0.08 and 0.55 mg/ml for O. ochengi after a 24 h incubation time. Preliminary phytochemical screenings on these extracts revealed the presence of flavonoids, alkaloids, saponins, carbohydrates and tannins in the extracts. Accordingly, application of A. leiocarpus, K. senegalensis, E. hirta and A. senegalensis extracts could provide alternatives in the control of helminthic infections.