Anti-embryonation immunity in murine schistosomiasis japonica (Philippines)

The hypothesis that granuloma modulation and disease abatement in chronic infection with Schistosoma japonicum could be ascribed to antibody-mediated effects on egg maturation and egg viability, arose from studies performed with mice in the Philippines. This novel hypothesis has not yet been integrated into the schistosomiasis literature despite being formulated more than a decade ago. One reason for this is that the phenomenon might be confined to S. japonicum, even S. japonicum (Philippines).

Evidence of anti-embryonation immunity and egg destruction in mice sensitized with immature eggs of Schistosoma japonicum.

BALB/c mice sensitized by repeated injections of immature eggs of the trematode worm, Schistosoma japonicum, were challenged with low numbers of cercariae and evidence was sought for inhibition of embryonation by examination of eggs in livers and intestines at days 40 - 42 of infection. In contrast to the situation in unsensitized control mice, a greater proportion of dead eggs was noted in tissues of many of egg-sensitized mice. There was also a decrease in the proportion of mature eggs relative to control mice. A substantial number of egg - sensitized mice contained no eggs in the liver though eggs were readily detected in their intestinal walls. The data support the concept that immune effector mechanisms act on eggs in a manner that prevents their full development into a miracidium and thus a rich source of immunopathologic antigens.

Schistosoma japonicum: the modulation of lung granuloma and inhibition of egg maturation in mice by human sera.

Human sera taken from patients with chronic schistosomiasis japonica have been demonstrated to have two effects on mice. Sera from those patients reduced the size of granuloma in mice sensitised for accelerated granuloma formation to eggs entrapped in the lungs of mice injected with the sera shortly before and at day 2 after intravenous egg challenge. The sera with this effect on the mouse lung granuloma models caused large segmented precipitates in the optimised circumoval precipitin test (COPT). Such sera also reduced the rate at which eggs matured in the liver and intestines of mice infected with S. japonicum. The results strongly support our postulate that a major cause of granuloma modulation in cases of chronic schistosomiasis japonica is antiembryonation immunity and that mice provide useful models for the analysis of our postulate. Identification of egg antigens responsible for the anti-embryonation effect should facilitate progress towards the development of a vaccine against granulomatous disease.

Resistance to reinfection with Schistosoma japonicum in the mouse.

BALB/c and outbred mice infected with a Philippine isolate of Schistosoma japonicum for 50 to 60 days expressed strong resistance to reinfection. The extent of this reinfection resistance ranged from 72 to 93% in 5 experiments (mean = 80% resistance) as determined by numbers of immature worms recovered from already infected and age- and sex-matched challenge control mice exposed 20 days previously to cercariae. Determination of numbers of recoverable worms from (the initial) infection suggest that adult worms are lost progressively during the period in which impressive resistance to reinfection is demonstrable. An important unresolved question is whether loss of adult worms is related in any way to expression of resistance to reinfection. Some indirect evidence indicates that the major component of reinfection resistance is expressed prior to day 4 of challenge infection. This evidence derives from analysis of lung petechiae which, in a primary infection, have been shown to provide an indication of number of adult worms which can be detected subsequently (e.g. at 30-40 days of infection). Although anti-parasite immune response have not yet been shown to be responsible for this apparent concomitant immunity, the magnitude of resistance to reinfection in the S. japonicum/mouse system should facilitate identification of any immunological effector mechanisms involved.

Attempts to standardize the circumoval precipitin test (copt) for Schistosomiasis japonica.

The circumoval precipition test (COPT) is a simple and inexpensive immunodiagnostic test for schistosomiasis japonica which, in the Philippines, has high sensitivity and specificity. Lack of standardization does, however, increase the variability of the test. Parameters which influence the COPT have been examined using large numbers of sera from known S. japonicum infected individuals. In this series of experiments, optimal conditions were determined to be as follows using 2 drops of neat serum and incubation at 37 degrees C in a sealed slide chamber; - approximately 100 eggs from 55 or 60 days infected rabbits for a 24 to 48 hour incubation period. COP reactions (i.e. precipitates associated with eggs) were much less obvious when either immature eggs or eggs obtained from long-term infected rabbits were used. The results emphasize the prime importance of the source of Schistosoma japonicum eggs in the performance of a standardized COPT.

Schistosoma japonicum: use of a radioimmunoassay for anti egg antibodies in human sera.

A solid-phase radioimmunoassay (RIA) was developed for schistosomiasis japonica using extracted egg antigens and compared with circumoval precipitin test (COPT) results on 20 sera from known S. japonicum-infected individuals and on 10 control sera. The quantitative RIA very clearly differentiated between infected and uninfected individuals with highest titers being obtained in teenagers. However, in the series employed, information relevant to immunodiagnosis of S. japonicum infection was contained in the non-quantitative but simple COPT and little was apparently added to the quantitative but expensive RIA.

Advances in pathophysiology of schistosomiasis japonica: a review.

Schistosomiasis is a chronic granulomatous disease caused by a delayed type of hypersensitivity reaction to eggs deposited or trapped in the tissues. Granuloma formation, depending on extent, if in the liver will lead to portal hypertension while if in the lungs, will lead to pulmonary hypertension and cor pulmonale.

The biology of Schistosoma japonicum, Philippine strain: a review.

Some important and adequately studied aspects of the biology of Schistosoma japonicum in the Philippines were reviewed and presented. The identity of the species of human blood fluke in the Philippines was established by Tubangui who also was the first to complete the life cycle of the parasite in his laboratory. Successful cross-infections of different strains of S. Japonicum from different mammalian hosts including man suggest that there is only one common strain for all of the definitive hosts in the Philippines. Studies on egg-laying habits, factors affecting hatching of eggs, eruption of cercariae from snails, cercarial survival and undocumented obervations are considered in this review.

The circumoval precipitin test in early experimental schistosomiasis japonica.

The time of the appearance of circumoval precipitins by testing weekly blood samples of rabbits infected with light, moderate and heavy doses of cercariae of Schistosoma japonicum as well as their titers were determined. In heavy infections, circumoval precupitins appeared as early as the end of the 4th week or 28th day after cercarial penetration while the appearance of detectable levels in light infections was delayed only up to the 7th week after infection. In view of these observations, the circumoval precipitin test should be used for detection of early schistosomal infection before eggs are demonstrable in the faeces.