The immune-dependence of chemotherapy in experimental schistosomiasis

Abstract

Experimental evidence indicates that immune effector mechanisms can enhance the activity of schistosomicidal drugs. Praziquantel, oxamniquine, hycanthone and antimony were less effective against Schistosoma mansoni infections in mice immunosuppressed by T cell-deprivation, than against comparable infections in normal mice. The schistosomicidal activities of praziquantel, oxamniquine and antimony have been experimentally enhanced by the synergistic action of immune sera. In passive serum transfer experiments a S. mansoni antigen of Mr 27kD with non-specific esterase activity was identified as a potentially sensitive target for the antibodies that interact with praziquantel. Indirect immunofluorescence indicated that this antigen was exposed on the worm surface as a result of praziquantel treatment.

Activity of Artemether and Mefloquine against Juvenile and Adult Schistosoma mansoni in Athymic and Immunocompetent NMRI Mice

“…5 Several antischistosomal drugs were found to have a reduced efficacy in immunosuppressed mice and immune effector mechanisms, particularly antibody, can enhance the activity of antischistosomal drugs. [6][7][8] The relevance of these experimental observations in mice to human disease is not known.…”

“…The antischistosomal drugs praziquantel, oxamniquine, hycanthone, and antimony are less effective in T-cell deprived mice 7 and the efficacy of praziquantel was found to be reduced in B-cell depleted mice. 8 An activation of drugs by the immune system has not only been described for antischistosomal drugs but also for other anti-parasitic treatments: for example, although the lack of B-cells did not impair the effect of the experimental drug toltrazuril in mice infected with Neospora caninum , T-cell immunity was found to be essential for full efficacy of treatment.…”

“…Another experimental antischistosomal drug, amoscanate was also not influenced by the absence of T cell-mediated immune responsiveness in mice. 7 It has been suggested that after praziquantel treatment, synergistically active antibodies gain access to key components of the morphologically damaged worm surface (mainly the membrane over the tubercles on the male worms), which is denied them by the normal undamaged worm surface. 7,18 The effects of mefloquine and artemether on the tegument of S. mansoni , on the other hand, show distinct differences when compared with praziquantel, 19,20 and antibodies may therefore not be able to interact with the tegument of mefloquine-and artemether-treated worms.…”

Studies of the mode of action of anthelmintic drugs: tools to investigate the biochemical pecularities of helminths

“…These antisera reacted most intensively in indirect immunofluorescence with the dorsal tubercles of drug-treated male worms. Further studies indicated that only selected antigens which are exposed through drug damage may be sensitive to immune attack (Doenhoff, 1989). These studies highlight the importance of multi disciplinary studies on the immune-dependence of chemo therapy.…”

“…The membrane over tubercles on the S. mansoni male dorsal surface is damaged and an increase in parasite-specific antigenicity is observed after in vitro treatment (Harnet and Kusel, 1986). Studies of Doenhoff (1989) revealed that the schistocidal activity of praziquantel was enhanced by the synergistic action of BIOCHEMICAL PECULARITIES OF HELMINTHS rabbit antisera. These antisera reacted most intensively in indirect immunofluorescence with the dorsal tubercles of drug-treated male worms.…”