Immune dependence of schistosomicidal chemotherapy: an ultrastructural study of Schistosoma mansoni adult worms exposed to praziquantel and immune serum in vivo.
This study examines the immune-dependence of praziquantel (PZQ) for the treatment of Schistosomiasis mansoni in mice. We have shown elsewhere from worm recovery data that the efficacy of PZQ is significantly enhanced when mice are treated concomitantly with antisera raised against antigens released from adult schistosomes, even though such antisera show no intrinsic helminthotoxic activity (Doenhoff et al. 1987, Doenhoff, Modha & Lambertucci 1988). Moreover, indirect immunofluorescence assays have shown that male worms exposed to the dual treatment regime in vivo bind antiserum to their dorsal surfaces in a pattern that seems to follow the outline of the dorsal tubercles. Scanning and transmission electron microscopy have now been used to further define the features of damage inflicted upon worms through exposure to antiserum alone, drug alone, or the two treatments in combination. Such investigations revealed that the antiserum induces a classical membrane repair process in worms of both sexes, but little other damage. PZQ causes the formation of spherical protuberances on the dorsal tubercles of male worms, while the dual treatment regime induces both kinds of damage in male schistosomes, but with much enhanced severity. The protuberances show evidence of explosion and some regions of the tegument become completely destroyed. Regions other than the dorsal surfaces of the male worms do not exhibit comparable trauma, and neither do the females. These data are discussed in relation to the known schistosomicidal activity of PZQ, the notion that male and female worms exhibit regional and sexual differences in susceptibility, documented evasive strategies of the parasite and the interdependence of immuno- and chemotherapy.
Modha
J
J
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, St Albans, Herts, UK.
Lambertucci
J R
JR
Doenhoff
M J
MJ
McLaren
D J
DJ
D000818:Animals; D000909:Antibodies, Helminth / Q000008:administration & dosage*; D000947:Antigens, Helminth / Q000276:immunology; D004357:Drug Synergism; D005455:Fluorescent Antibody Technique; D007109:Immunity; D051379:Mice; D008808:Mice, Inbred CBA; D011223:Praziquantel / Q000494:pharmacology*; D011817:Rabbits; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000276:immunology
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D011223:Praziquantel