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Schistosoma mansoni is a parasitic trematode of the portal-mesenteric veins with a closed-end intestine. Adult worms regurgitate their intestinal content after digestion, together with constituents of the lining gut. Some of these molecules circulate in the blood and are antigenic. We obtain a "vomit" preparation and preliminary evaluate its biochemical composition and antigenic capacity. The "vomit" preparation was obtained after changes in temperature and solutions of incubation of adult worms between 4 and 37 degrees C. Supernatant was assayed for protein, carbohydrate concentration and enzymatic activities associated to the intestine and to the worm tegument. The antigenicity of the product was evaluated using Western blot (WB) analysis against sera of experimentally infected mice, before and after drug cure, sera from people infected with S. mansoni and from individuals infected with other parasitoses. More carbohydrate than protein was detected in the preparations. Cysteine proteinase (CP), N-acetyl-beta-D: -glucosaminidase and alkaline phosphatase activities were detected. The latter enzyme activity is a marker of the tegument, suggesting that in spite of careful conditions used to avoid the presence of tegumental material, manipulation of the worms always resulted in the release of tegumental molecules. Cationic exchange chromatography was useful to separate various components of this "vomit" preparation, particularly enzymes responsible for CP activity. Two highly immunogenic and specific duplets were observed in the WB analysis, 31/32- and 38/40-kDa components, the former probably referring to the intestinal CPs Sm31/Sm32. None of the two duplets disappeared after successful chemotherapy during the time of evaluation in mice or humans.

The efficacy of different treatment protocols in humans infected with Schistosoma mansoni at sites with different transmission conditions was evaluated by the disappearance of anti-worm intestine IgM antibodies in an indirect fluorescence antibody test (IgM-IFT) and anti-egg antibodies in the circumoval precipitin test (COPT). Patient sera coming from sites of active low transmission (ALT), active high transmission (AHT) and low interrupted transmission (LIT) from Venezuela were studied. Chemotherapy protocols were (1) ALT, 60 mg/kg praziquantel (Pzq60); (2) AHT, one dose of 40 mg/kg Pzq followed by one dose of 20 mg/kg oxamniquine for one group and one dose of 40 mg/kg Pzq alone for the other group; (3) LIT, one dose of 40 mg/kg Pzq repeated every 3 months up to three doses. Cure rates occurred mostly between 3 and 12 months with the exception of Pzq60-ALT where it was evident before 3 months. Higher cure rates were evident in both places of low transmission (ALT and LIT) and the lowest in the AHT regardless of the treatment protocol. Cure was more evident with COPT compared to IgM-IFT. The rate of serological cure appears then to depend on the previous state of transmission. The differential cure rate evaluated by both techniques is probably due to the persistence of antibodies against antigens in different stages of the parasite.

For evaluation of the degree of genetic heterogeneity in parasite and snail strains, the compatibility between Biomphalaria glabrata and Schistosoma mansoni from different geographical areas was studied. Venezuelan snails from Bárbula, Manuare (areas of schistosome transmission) and Tinaquillo (non-transmission area) and Brazilian BH snails were exposed to infection with miracidia of both the Venezuelan YT and SM strains and the Brazilian BH strain of S. mansoni. Snail-parasite compatibility was evaluated by quantifying the number of snails shedding cercariae during a period of 35 to 60 days post-infection. The best compatibility appeared to be between the Brazilian parasites and the Brazilian or Venezuelan snails. In contrast, the Brazilian snails appeared to be resistant to infection by the Venezuelan parasites tested. Paradoxically, the compatibility between the sympatric pair of Venezuelan parasites and Venezuelan snails appeared to be lower in comparison with the allopatric association of the Brazilian parasite and the Venezuelan snails. The results suggest an important degree of heterogeneity in the snail and parasite isolates studied and yield biological markers for both organisms.

The susceptibility of two Venezuelan (YT and SM) and one Brazilian (BH) strain of Schistosoma mansoni to single oral doses of praziquantel (Pz; 250 or 500 mg/kg), oxamniquine (Ox; 40, 60, or 100 mg/kg) or to low-dose combinations of both drugs (33 mg/kg Pz and 25 mg/kg Ox; 66 mg/kg Pz and 12.5 mg/kg Ox; 250 mg/kg Pz and 40 mg/kg Ox) was experimentally evaluated in mice. At lower doses of either drug, adult worms of the SM isolate were less susceptible than those of the BH and YT isolates. However, no difference in liver or intestinal egg counts (IECs) could be detected among the isolates after this treatment. At such doses, Pz was better than Ox at reducing IECs. In spite of lowered IECs, eggs continued to accumulate in the liver after Ox treatment. At higher individual doses or following treatment with low-dose combinations of both drugs, no difference in susceptibility could be detected among the parasite isolates. Under such conditions, oviposition was drastically reduced in all three isolates. We confirm that Ox preferentially kills male parasites and present for the first time evidence for the preferential killing of female worms by Pz. We propose that the synergistic effect obtained in the present study and in other investigations using low-dose combinations of both drugs may be due to the preferential cytotoxicity of each drug against a different parasite sex.