Genetic analysis of praziquantel resistance in Schistosoma mansoni

To determine the genetic basis of the resistance of Schistosoma mansoni to praziquantel (PZQ) and to understand whether the resistance is dominant or recessive trait, a schistosome cross was undertaken between a PZQ-susceptible and a PZQ-resistant isolate using infections of the single-sex cercariae which were identified by a direct W1-specific PCR technique. The resistances of F1 and F2 generation to PZQ were evaluated using in vitro egg, miracidial and cercarial tests. The F1 hybrid progeny from crosses between the susceptible and resistant isolates were resistant to PZQ. The resistant phenotype reappeared in the F2 progeny. It can thus be considered that the PZQ resistance behaves like a dominant trait.     

Schistosoma mansoni eggs in urine

S. mansoni eggs show a preferential localization in stools with localization in urine being unusual. The factors that influence the appearance of S. mansoni in urine have not been studied extensively. The data presented here were collected during a schistosomiasis survey conducted in the northern provinces of Cameroon and a longitudinal community survey in Douloumi. As expected, the majority of individuals infected with S. mansoni had eggs in their stools. However, this is not always the case. Under special epidemiologic conditions, very high S. haematobium prevalence and much lower S. mansoni prevalence, urinary localization may become dominant. Individuals with high intensities of infection by S. mansoni do not have a higher probability for having S. mansoni in urine (there is no 'spill over').     

Hybridization of Schistosoma mansoni and Schistosoma japonicum in mice

Crossing experiments in mice with two human species of Schistosoma japonicum (Taiwan strain) and Schistosoma mansoni (Puerto Rican strain) were performed. The hybrid miracidia from the cross between female S. japonicum and male S. mansoni infected both Biophalaria glabrata and Oncomalania h. chiui. However, those from the reciprocal crossing could infect only B. glabrata. B. glabrata infected with hybrid miracidia of female S. mansoni x male S. japonicum survived up to 30 days while those infected with miracidia of S. mansoni remained alive for more than 100 days after the first shedding of cercariae. Relatively few hybrid eggs reached maturity either in tissues or in the feces of infected mice. A low percentage of F1 eggs hatched and the infectivity of F1 miracida was also low. Morphology and behavior of hybrid eggs, miracidia, cercariae, and adults were similar to the maternal species. The daily egg production of the hybrid worm pair was less than that of the normal one. The observations in the present study may be attributed to the maternal effects. However, the phenomenon of parthenogenesis in schistosomes cannot be confirmed.     

Induction of resistance to Schistosoma mansoni by immunization with subfractions of worms

Induction of resistance to a Schistosoma mansoni infection was analyzed following injections of glutaraldehyde-fixed parasites or of subfractions prepared from nonfixed parasites killed by repeated freeze-thaw cycles. The parasites were isolated from mice infected 4 weeks previously and the subfractions were prepared by extraction in buffered saline or in detergent. A variety of immunization protocols were conducted in rats and mice. These included different sites of injection, dose size, and number of booster injections; different adjuvants; and the effects of boosting with live infections. Induction of a partial resistance is observed in rats, but has not been achieved in mice immunized by the same procedures. The alum-precipitated detergent-solubilized fraction was superior at lower doses. Exposure of rats to a low dose cercarial infection 3 weeks prior to challenge did not boost the resistance if the rats were already partially resistant through vaccination with worm subfractions in adjuvant. Serum from vaccinated rats transfers partial protection to a challenge infection of naive rats.     

Examination of the mechanisms of pulmonary phase resistance to Schistosoma mansoni in vaccinated mice

Potential mechanisms causing elimination of lung stage schistosomula were investigated in normal C57BL/6 mice and C57BL/6 mice previously vaccinated with irradiated cercariae. Autoradiography was used to measure the proportion of radiolabeled schistosomula which could be recovered from lung tissue by mincing and incubation. There was no difference between the two sets of mice at each time point, and no substantial diminution in the proportion recovered over the sampling period of 7 to 17 days post-infection. By this in vitro criterion, the emergence of schistosomula from lung fragments was not influenced by inflammation. However, we are unable to rule out the possibility that migration is impeded by inflammation in vivo. The migratory potential and viability of schistosomula recovered after residence in the lungs for increasing lengths of time was assessed by their introduction into the vasculature of naive recipients. The results indicate that significant numbers of schistosomula are capable of maturation, but fail to mature if left in situ in the lungs of both normal and vaccinated mice. No evidence was found that schistosomula suffer cytotoxic injury in the skin, subsequently dying in the lungs, or that they are damaged by the pulmonary inflammatory reactions which develop in vaccinated mice. Schistosomula delivered to the alveoli have a limited capacity to reenter tissues and mature. We suggest that in normal C57BL/6 mice the deflection of parasites into the alveoli during migration is the reason why many fail to mature. In vaccinated C57BL/6 mice a similar but augmented process may account for the elimination of a greater proportion of challenge parasites.