Effective schistosomicidal action of praziquantel against Schistosoma mansoni infections in mice appears to be dependent to some extent on appropriate immunological stimulation. Indirect evidence consistent with this hypothesis was obtained by demonstrating a positive relationship between drug efficacy and both the intensity and the age of the parasitic infection. More directly, it has previously been shown that praziquantel kills fewer S. mansoni worms in immunosuppressed T cell-deprived mice than in immunologically intact controls; and we show here that infections 5 weeks old, against which the drug alone is sub-optimally active, are more effectively killed by a combination of drug and a rabbit antiserum raised against adult worm antigens.
T-cell deprived mice heavily infected with Schistosoma mansoni suffer from severe microvesicular damage to hepatocytes within seven weeks of infection. The damage can be prevented by administration of serum (CIS) obtained from mice chronically infected with S. mansoni or from mice immunized with intact or homogenized S. mansoni eggs. Reaction of serum samples from individual chronically infected mice in immunoelectrophoresis with S. mansoni egg homogenate has enabled the identification of at least 12 distinct immuno precipitation reactions. Precipitating antibody against one S. mansoni egg antigen, omega 1, has been detected in all mice with patent chronic infections, and anti-omega 1 antibody is the most concentrated of the precipitating anti-egg antibody species in pooled CIS. Pooled serum obtained from infected intact mice reacting predominantly against omega 1 was found partially to prevent the hepatotoxicity reaction on transfer to infected deprived mice. Serum samples from mice injected with egg homogenate fractionated either by preparative electrophoresis or by cation exchange chromatography, and containing antibodies reactive with antigen omega 1 in immunoprecipitation, were fully protective against liver cell damage induced by S. mansoni in deprived mice. Sera from mice immunized with other S. mansoni egg fractions, and which did not contain antibodies reactive with omega 1, were not hepatoprotective. Antigen omega 1 is compared and contrasted with other S. mansoni egg antigens that have been described.
Within seven weeks of infection with 200 Schistosoma mansoni cercariae, T-cell deprived mice have been shown to suffer from extensive microvesicular damage to hepatocytes, and an inability to excrete parasite eggs at the same rate as comparably infected, immunologically intact controls. Administration of serum (CIS) from chronically infected, immunologically intact donors prevented the development of microvesicular cell damage and partially restored egg excretion rates in infected deprived mice. Serum pools obtained from mice injected either with intact S. mansoni eggs or with a homogenate of eggs emulsified in Freund's complete adjuvant (FCA) were as effective as CIS in preventing hepatotoxicity and restoring the rate of egg excretion in infected deprived recipients. The degree of protection of liver tissue afforded by immune sera could be monitored either by histopathological examination of liver sections or by estimation of serum transaminase concentrations, the results from both assays being generally in agreement. Sera from donor mice injected with cercarial or worm antigens in FCA were relatively inactive either in protecting against S. mansoni-induced liver damage or in reconstituting egg excretion rates in infected deprived mice. Serum from donor mice infected with 25 cercariae became hepato-protective between 49 and 53 days after infection of the donors, and the degree of hepatoprotective activity and egg excretion reconstituting capacity in the serum of 25 cercariae-infected donors was shown to increase between 8 and 16 weeks after infection. Increasing the size of infection of the serum donors to 100 cercariae gave only a marginal increase of hepatoprotective activity at 7 weeks when compared with serum donors infected with 25 cercariae for 7 weeks. Liver parenchymal cells of very heavily infected, immunologically intact mice were found to show microvesicular damage similar to that in livers of infected deprived mice, and administration of CIS to these normal mice was histopathologically protective. However, the elevated serum transaminase concentrations obtaining in the infected normal mice were not reduced to any extent by CIS. The results obtained from serum-reconstituted deprived mice are discussed in terms of the contribution they may make to a better understanding of the host-parasite relationship in immunologically intact mice.
The degree of resistance acquired by Schistosoma mansoni-infected mice against homologous challenge has been determined by perfusion of the animals within three weeks of the challenge, at which time the challenge-derived organisms were morphologically distinguishable from the primary infection which induced the resistance. The method has been compared with assays based on determination of the number of organisms migrating through the lung, and with perfusions at a later time when the challenge has matured. The results obtained with the three week perfusion method, showing that resistance was acquired by eight weeks after a primary infection, were confirmed by the longer survival of, and reduced egg excretion rates and tissue egg burdens in the experimental animals relative to respective challenge control animals. However, some discrepancy in challenge-derived worm numbers was found between animals perfused three weeks after challenge and those autopsied at later times. The possible reasons for this difference are discussed. The degree of resistance that was acquired was to some extent dependent on the size of the challenge infection.
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