Cytokine mRNA profiles in pigs exposed prenatally and postnatally to Schistosoma japonicum.

The pig is a natural host for Schistosoma japonicum and a useful animal model of human infection. The aim of the present study was to assess the differences between the cytokine profiles in prenatally or postnatally S. japonicum exposed pigs. Seven prenatally exposed pigs, 7 postnatally exposed pigs and 4 uninfected control pigs were compared 27 weeks post exposure. Variables included worm burdens, tissue egg counts, liver pathology and mRNA levels of IL-2, IL-4, IL-10, IL-12, TNF-alpha, TGF-beta1 and IFN-gamma in the liver and the caecum, assessed by RT-PCR. Infection intensity and level of septal fibrosis were significantly higher in the postnatal group compared to the prenatal group (P < 0.05). A significant increase of IL-4 (P < 0.01), IL-10 (P < 0.01), IL-12 (P < 0.01) and TNF-alpha (P < 0.05) mRNA level was also observed in the caecum of prenatally infected animals compared to the control group (P < 0.01). The prenatal group showed higher levels of TGF-beta1 in the liver compared with the postnatally infected group (P< 0.05) and the control group (P< 0.01). This suppressive immune response correlated with previously reported low hepatic pathogenesis in prenatally exposed pigs.

Congenital infection of rabbits with Schistosoma japonicum and protective immunity of offspring.

BACKGROUND: Recently congenital infection with Schistosoma japonicum (S. japonicum) has been demonstrated in pigs, rabbits, mice and dogs. We explored the rabbit as an animal model for the congenital infection of schistosomiasis japonica and assessed the effect of a congenital S. japonicum infection on the resistance of rabbit kittens to a postnatal challenge infection. METHODS: Sixteen pregnant New Zealand white rabbits were infected with a single dose of S. japonicum cercariae. The exposed animals were divided into three groups according to the gestation age at the time of infection. Diagnosis of prenatally acquired S. japonicum infection in the rabbit kittens was primarily based on serological tests in combination with parasitological and histopathological findings. Congenitally infected kittens were challenged percutaneously with 100 S. japonicum cercariae to assess the effect of a congenital S. japonicum infection on kitten resistance to a postnatal challenge infection. RESULTS: The overall prevalence of congenital infection in offspring of infected mothers was 20% (12/60). The congenital infection rate in group L (late gestation) was much higher than in group E (early gestation) and group M (mid-gestation) (P <0.05). After a postnatal challenge infection, prenatally infected kittens had a 54.66% worm reduction rate, 41.45% egg reduction rate, and 51.76% granuloma size reduction rate compared to naïve kittens. CONCLUSIONS: This study demonstrates the possibility of congenital infection of S. japonicum in rabbits and the resistance of congenitally infected kittens to a postnatal challenge infection. These results have important implications not only for epidemiological investigations, but also in designing government control programs for schistosomiasis.

Prenatal Schistosoma japonicum infection in piglets: effect of repeated exposure of the dams on treatment efficacy and susceptibility to challenge infections.

This study elucidated the fate of prenatal infections in piglets born by dams repeatedly infected before and during pregnancy with Schistosoma japonicum. Independent variables included repeated infections of the dams and treatment or challenge infection (or both) of the prenatally exposed piglets. Dependant variables were worm counts, fecal and tissue egg counts, weight gain, and gross pathological observations. Fifteen female piglets (the dams) were included, of which 6 received repeated infections with S. japonicum during 6 mo. All dams were inseminated and 10 wk pregnant; 12 of the dams were infected with S. japonicum, of which 6 had been repeatedly infected. Three dams remained uninfected. Eight weeks after delivery, the prenatally exposed piglets (the offspring) were grouped, and 6 of the 12 groups were treated with praziquantel. Four weeks after treatment, 5 groups of piglets were infected with S. japonicum. Groups of piglets were killed either 12 or 22 wk after delivery. Repeated infections of the dam did not prevent establishment of a congenital infection in the pig fetuses. Piglets born with a congenital infection were not resistant to a S. japonicum challenge infection given 12 wk after birth. Neither did praziquantel effectively cure the piglets nor did treatment of the prenatally infected piglets prevent establishment of a challenge infection given 4 wk after treatment. Results of the present study indicate that prenatal exposure, independently of the dam's infection status, may change the host response to challenge infections and treatment after birth.

Pathogenesis of congenital infection with Schistosoma japonicum in pigs.

To elucidate aspects of pathogenesis of congenital infections with Schistosoma japonicum, 5 Danish crossbred sows were infected during late pregnancy with a Chinese isolate of S. japonicum, and 17 of their offspring (fetuses and piglets) were examined 7, 20. 34, 54, and 69 days postinfection (PI). Organ samples were collected for histopathological examination with emphasis on liver and lung. Samples of the corresponding placenta were also collected from fetuses at postmortem examinations. Perfusions were performed on some of the fetuses to recover schistosomes, and in addition, amniotic fluid was examined for schistosomes. A schistosomulum was found in a 99-day-old fetus 3 wk PI. Eggs were found in meconium from 109-day-old fetuses 34 days after infection of the dam, showing that the prepatent time was the same as in postnatal infections. Piglets examined 54 and 69 days PI had inflammatory reactions in their livers, and progression toward healing and repair of the inflammatory reaction occurred from 54 to 69 days PI. This pilot study is one of the bases for the model of congenital schistosomiasis used currently at the Danish Centre for Experimental Parasitology.

Congenital infection with Schistosoma japonicum but not with Schistosoma bovis in sheep.

The present study investigated whether Schistosoma japonicum or Schistosoma bois could establish prenatally in lambs. Three ewes were exposed to S. japonicum by intramuscular injection of cercariae, and 3 ewes were exposed to S. bovis cercariae using the leg-emerging technique approximately 2 mo before delivery, and 1 age-matched pregnant ewe served as an uninfected control. The study lasted 18-20 wk after infection, which was 8-9 wk after delivery. All 6 exposed ewes became infected with either S. bovis or S. japonicum. Eight lambs were borne by the 7 ewes, of which 1 (S. bovis exposed) was dead and 1 (S. japonicum exposed) died at delivery. Of the 3 S. japonicum-exposed lambs, 2 were found infected. Four lambs born of S. bovis-exposed ewes were negative. Despite having no worms, these 4 S. bovis-exposed lambs as well as the 1 negative S. japonicum-exposed lamb had, in contrast to the nonexposed control lamb, few, but distinct, liver granulomas dominated by eosinophils and giant cells with large central necrotic areas but with no remnants of eggs or worms. Hence, congenital infection was demonstrated in S. japonicum-infected lambs, but not in S. bovis-infected ones.

Postnatal challenge infections of congenitally Schistosoma japonicum-infected piglets.

The aim of the present study was to assess the effect of a congenital Schistosoma japonicum infection on the establishment, fecundity, and pathogenicity of a postnatal challenge infection. Five prenatally S. japonicum-infected piglets received a challenge infection (prenatal + challenge group), 5 prenatally infected piglets were followed without challenge (prenatal group), and 10 piglets, born by unexposed sows, served as challenge controls (challenge control group). Challenge infections were given 8 wk after the piglets were born (14 wk after the primary infection of the sows), and the study lasted another 11 wk. Variables included worm burden, tissue egg count, and liver pathology. Worm establishment and tissue egg count were comparable in the prenatal + challenge group and in the challenge control group, both exceeding at a statistically significant level those in the prenatal group. No difference in worm fecundity (eggs/female worms/g tissue) was seen between the 3 groups. Liver pathology (i.e., portal and septal fibrosis) was more severe in the challenge control group compared to the other groups. A congenital S. japonicum infection in piglets thus affected neither establishment nor fecundity of a postnatal challenge infection. In spite of this, the challenge infection gave rise to much less liver pathology than the similarly sized challenge control infection.

Schistosoma japonicum infection in pregnant mice.

Ten 1-week and ten 2-weeks pregnant female NMRI mice were experimentally exposed to 70 Schistosoma japonicum cercariae. Ten littermice from each group were examined for worms by perfusion 4, 6 and 8 weeks post infection. Although the mothers (n = 15) were found infected with 15.5 +/- 13.4 worms at perfusion 6 and 7 weeks post infection, no worms were found in any of the examined littermice, as well as no detection of faecal or tissue eggs. Litter sizes did not differ from control groups and all littermice were healthy. The present study therefore suggests that congenital infection with S. japonicum does not occur in percutaneously infected mice and that infection of the mother during pregnancy does not seem to affect the offspring.

Congenital transmission of Schistosoma japonicum in pigs.

Congenital transmission of Schistosoma japonicum in pigs was investigated by experimentally infecting sows at four weeks gestation (n = 3), 10 weeks gestation (n = 3), or a few weeks prior to insemination (n = 2). None of the piglets born to sows infected prior to insemination or in early pregnancy were found to be infected. However, all of the piglets (n = 26) born to sows infected at 10 weeks gestation were found to harbor schistosomes with S. japonicum eggs recovered from both their feces and livers. The findings show that congenital S. japonicum infection of pigs can occur if sows are infected during mid-to-late pregnancy and may have important implications not only for pigs but also for other mammalian hosts of schistosomes, including humans.