Drug-induced exposure of Schistosoma mansoni antigens SmCD59a and SmKK7

• Published in: PLoS neglected tropical diseases 2015-03, Vol.9 (3), p.e0003593-e0003593
• Main Authors: Reimers, Natalie, Homann, Arne, Höschler, Beate, Langhans, Kristina, Wilson, R Alan, Pierrot, Christine, Khalife, Jamal, Grevelding, Christoph G, Chalmers, Iain W, Yazdanbakhsh, Maria, Hoffmann, Karl F, Hokke, Cornelis H, Haas, Helmut, Schramm, Gabriele
• Format: Article
• Language: English
• Subjects: Animals; Anthelmintics; Anthelmintics - pharmacology; Antigen presentation; Antigens; Antigens, Helminth - analysis; Artemisinins - pharmacology; CD59 Antigens - analysis; Developing countries; Dosage and administration; Drug therapy; Drugs; Experiments; Health aspects; Humans; LDCs; Male; Morphology; Parasites; Parasitic diseases; Praziquantel - pharmacology; Rats; Rats, Inbred BN; Rats, Inbred F344; Schistosoma mansoni - drug effects; Schistosoma mansoni - immunology; Schistosomiasis; Studies; Tropical diseases
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0003593

Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during worm development. Anthelmintic drugs have been tested mainly on adult schistosomes or freshly transformed cercariae. Knowledge concerning the larval stages is lacking. In this study, we used in vitro-grown schistosomula (aged between 2 to 14 days) to investigate drug effects of the three anthelmintics praziquantel, artemether, and oxamniquine. Further, we analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a and SmKK7, before and after drug treatment. Our results demonstrated that praziquantel applied at a concentration of 1 μM inhibited development of all life stages. Application of 10 μM praziquantel led to dramatic morphological changes of all schistosomula. Artemether at 1 and 10 μM had differential effects depending on whether it was applied to 2-day as compared to 7- and 14-day schistosomula. While 2-day schistosomula were not killed but inhibited from further development, severe morphological damage was seen in 7- and 14-day schistosomula. Oxamniquine (1 and 10 μM) led to severe morphological impairment in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7 before drug treatment showed no antibody binding on living intact schistosomula. However, when schistosomula were treated with anthelmintics, both antigens became exposed on the larvae. Oxamniquine turned out to be most effective in promoting antibody binding to all schistosomula stages. This study has revealed marked differences in anthelmintic drug effects against larvae. Drug treatment increases surface antigen presentation and renders larvae accessible to antibody attack.