1999 by The American Society of Tropical Medicine and Hygiene. SHORT REPORT: CONGENITAL TRANSMISSION OF. SCHISTOSOMA JAPONICUM IN PIGS.
Am. J. Trop. Med. Hyg., 60(2), 1999, pp. 311–312 Copyright q 1999 by The American Society of Tropical Medicine and Hygiene
SHORT REPORT: CONGENITAL TRANSMISSION OF SCHISTOSOMA JAPONICUM IN PIGS A. LEE WILLINGHAM III, MARIA V. JOHANSEN, HENRIK O. BØGH, AKIRA ITO, JØRN ANDREASSEN, RONNY LINDBERG, NIELS Ø. CHRISTENSEN, AND PETER NANSEN Danish Centre for Experimental Parasitology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark; Danish Bilharziasis Laboratory, Charlottenlund, Denmark; Department of Parasitology, Asahikawa Medical College, Asahikawa, Japan; Department of Population Biology, University of Copenhagen, Copenhagen, Denmark; Department of Pathology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden
Abstract. Congenital transmission of Schistosoma japonicum in pigs was investigated by experimentally infecting sows at four weeks gestation (n 5 3), 10 weeks gestation (n 5 3), or a few weeks prior to insemination (n 5 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 5 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. natal deaths in piglets from Group E sows (36% [14 of 39] compared with 7% [2 of 28] and 11% [2 of 19] in Groups M and P, respectively), although this was not statistically significant. Surviving piglets from group E generally were smaller, weaker, and less vigorous than piglets from groups M and P based on subjective observations. Examination of piglet feces, which was conducted every two weeks, revealed S. japonicum eggs only in Group M piglets, with the first eggs appearing two weeks after birth. Fecal egg counts were mostly , 10 eggs/g of feces, although high counts ranging from 222 to 339 eggs/g of feces were noted five weeks after birth (11 weeks after sow exposure) for three piglets from the same litter. All piglets in Group P and three randomly selected piglets from each sow in Groups E and M were examined for worms 5–6 weeks after they were born.7 Remaining piglets in Group E and M litters were examined for worms 11 weeks after birth. Schistosomes were recovered from all 26 Group M piglets; however, no worms were recovered from any of the 25 Group E piglets or the 17 Group P piglets. No significant difference was found between mean total worm burdens of Group M piglets at the two worm collection times (Table 1), although there was considerable variability, as we have seen with infections of adult pigs.6,7 Schistosome eggs were recovered from the livers of all Group M piglets and histopathologic examination of liver sections taken at five weeks after birth showed a granulomatous response to the eggs consistently in portal areas as in postnatally infected mammals (Figure 1). We also found periportal fibrosis in the livers of piglets from Group M perfused 11 weeks after birth. All sows were treated with praziquantel (50 mg/kg orally) after weaning of piglets. Our experimental findings show that congenital transmission of S. japonicum can occur in pigs during the latter half of pregnancy; an important finding not only for pigs but also perhaps for other hosts including humans. Pigs have an epitheliochorial placenta composed of six layers (three uterine and three fetal), while humans have a hemomonochorial placenta composed of only three separating layers.8 Thus, one could expect the porcine placenta to serve as a more complete barrier between the maternal and fetal circulations. To our knowledge, the only systematic studies that have been
Schistosomes are generally considered to infect their hosts percutaneously, but Japanese researchers early this century1,2 and again in the 1950s3,4 also suggested the likelihood of congenital infection by Schistosoma japonicum. However, the results of their studies appear to have been ignored for several decades. Narabayashi1 recovered juvenile schistosomes from newborn dogs, rodents, and rabbits whose mothers had been experimentally infected while pregnant. Also of particular note was the finding of schistosome eggs in the feces of newborn children with no history of water contact, but whose mothers had a history of possible exposure to S. japonicum from working in rice fields while pregnant.2 In l957, Kikuchi3 demonstrated experimental congenital infections of two goat kids born to mothers infected during late gestation. The Japanese findings are supported by Chinese studies5 in which adult schistosomes have been recovered from aborted calf fetuses, and newborn calves and water buffaloes have been found to pass S. japonicum eggs in their feces. We hereby report that the pig, an important natural host of S. japonicum, can become infected in utero with the parasite. To investigate the congenital schistosomiasis phenomenon, sows were experimentally infected in early or mid-gestation, or while not pregnant a few weeks prior to insemination, using an infection method involving minimal handling in recognition of their large size (. 500 lbs) and advanced pregnancy of some pigs. Eight specific pathogen-free Landrace-Yorkshire-Duroc cross-bred sows were injected intramuscularly with approximately 9,000 medium-suspended cercariae of a Chinese isolate of S. japonicum,6 expecting about 10% worm establishment. Three of these sows (Group E) were in early pregnancy (four weeks gestation), three (Group M) were in mid-pregnancy (10 weeks gestation), and the other two (Group P) were nonpregnant pigs that were inseminated two weeks later. All pigs in the experiment were treated in accordance with animal ethics laws of Denmark. Schistosoma japonicum eggs were recovered from feces7 of all sows from six weeks after injection onwards (range 5 91–584 eggs/g of feces with maximum egg counts of individual pigs from different groups overlapping), yet none became clinically ill. Gestation periods lasted the normal 16 weeks. We found a high percentage of stillbirths and neo-
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TABLE 1 Mean 6 SE worm counts of piglets congenitally infected from mothers given 9,000 cercariae of Schistsoma japonicum at 10 weeks gestation (Group M)* Perfusion time after birth 5 weeks (n 5 9)
Female worms Male worms Immature worms Total worms
8.8 9.2 1.4 19.4
6 6 6 6
3.60 3.87 0.41 7.41
10 weeks (n 5 17)
3.3 4.3 0.4 8.0
6 6 6 6
1.10 1.02 0.19 2.04
* The Student’s t-test was used to compare group means.
conducted on schistosomiasis in newborn humans or livestock are reviewed here. Apparently no published information exists on congenital infection with other schistosomes of humans (e.g., S. mansoni, S. haematobium). The probability in endemic areas that S. japonicum could often cross the human placenta but remain undetected seems high since infants are seldom included in surveys. Congenital infection may have important implications for the pathogenesis of schistosomiasis japonica. In particular, the effect of parasitism on the prenatal and infantile host’s developing immune system, especially with regard to resistance and tolerance, should be investigated as well as consequences for the population biology of schistosomes and the epidemiology of schistosomiasis. Our findings warrant further exploration of the mechanisms and impact of congenital schistosomiasis.
Acknowledgments: We thank Lisbeth Pedersen and Niels Peter Hansen for technical assistance. Financial support: This study was funded by the Danish National Research Foundation. Authors’ addresses: A. Lee Willingham III, Henrik O. Bøgh, and Peter Nansen, Danish Centre for Experimental Parasitology, Royal Veterinary and Agricultural University, Ridebanevej 3, DK-1870 Frederiksberg C, Denmark. Maria V. Johansen and Niels Ø. Christensen, Danish Bilharziasis Laboratory, Jaegersborg Alle´ 1 D, DK2920 Charlottenlund, Denmark. Akira Ito, Department of Parasitology, Asahikawa Medical College, Asahikawa 078, Japan. Jørn Andreassen, Department of Population Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark. Ronny Lindberg, Department of Pathology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Box 7028, S-75007 Uppsala, Sweden.
FIGURE 1. Egg granuloma in the liver of a piglet born to a sow infected with Schistosoma japonicum at 10 weeks pregnancy displaying epithelioid macrophages, giant cells, and lymphocytes surrounding a schistosome egg (hematoxylin and eosin stained, original magnification 3 200). REFERENCES
1. Narabayashi H, 1914. Demonstration of specimens of Schistosoma japonicum: congenital infection and its route of invasion (in Japanese). Kyoto Igaku Zasshi 11: 2–3. 2. Narabayashi H, 1916. Contribution to the study of schistosomiasis japonica (in Japanese) Kyoto Igaku Zasshi 13: 231–278. 3. Kikuchi S, 1957. Studies on placental infection of Schistosoma japonicum. Sogo Igaku 14: 537–554. 4. Sakamoto H, 1958. The influence of schistosomiasis japonica from the gynecologycal aspect (in Japanese) Kurume Igakkai Zasshi 21: 2361–2383. 5. Wang XY, 1959. Abortions in cattle (in Japanese). Ministry of Health, People’s Republic of China, ed. Control of Domestic Animal Schistosomiasis. Shanghai: Shanghai Science and Technology Press, 141–151. 6. Willingham AL, Bøgh HO, Vennervald BJ, Johansen MV, Eriksen L, Christensen NØ, Nansen P, 1996. Worm establishment and egg production of Schistosoma japonicum in pigs infected by percutaneous methods or intramuscular injection. Vet Parasitol 61: 157–163. 7. Willingham AL, Hurst M, Bøgh HO, Johansen MV, Lindberg R, Christensen NØ, Nansen P, 1998. Schistosoma japonicum in the pig: the host-parasite relationship as influenced by the intensity and duration of experimental infection. Am J Trop Med Hyg 58: 248–256. 8. Dantzer V, Bjo¨rkman N, 1993. Placentation. Dellman HD, ed. Textbook of Veterinary Histology. Philadelphia: Lea & Febiger, 255–269.
