Placental and Oral Delivery of Schistosoma Mansoni Antigen From Infected Mothers to Their Newborns and Children

Attallah, Abdelfattah M.; Ghanem, G.; Ismail, Hisham; Waseef, Ahmed M. El

doi:10.4269/ajtmh.2003.68.647

Cited by 42 publications

(35 citation statements)

References 18 publications

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“…The transplacental transport of soluble egg and adult worm antigens and their detection in the newborn have been documented in multiple reports (4,9,24,31,46,49). For example, Hassan et al detected an S. mansoni carbohydrate antigen in 66% of the urine samples from newborns of S. mansoni-infected mothers (n ϭ 45) (24).…”

Section: Discussionmentioning

confidence: 99%

Maternal Schistosomiasis Japonica Is Associated with Maternal, Placental, and Fetal Inflammation

Kurtis

Higashi

et al. 2011

Infect Immun

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Schistosomes infect ϳ40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial in Schistosoma mansoni did not detect this association. We conducted an observational study among 99 pregnant women living in an area of Schistosoma japonicum endemicity in the Philippines. We enrolled women at 32 weeks gestation and measured S. japonicum and geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-␣] and interleukin 10 [IL-10]), placental (TNF-␣, IL-6, TNF-␣ receptor II [RII], and IL-1␤), and cord (IL-1␤ and TNF-␣ RII) blood, as well as acute subchorionitis and increased TNF-␣ production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1␤, and TNF-␣ production by syncytiotrophoblasts was independently associated with decreased birth weight (both P < 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.Healthy successful pregnancies are characterized by a placental microenvironment that is biased toward a T-helper cell type 2 (Th2) cytokine milieu (16,23). Parasitic diseases, including malaria and leishmaniasis, alter the placental Th2 bias toward a proinflammatory microenvironment and are associated with poor pregnancy outcomes (29,39,48). These data are consistent with animal models of pregnancy that establish that increased systemic and placental gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) levels produce poor pregnancy outcomes (10, 50). They are also consistent with the marked increase in prematurity and IUGR accompanying human pregnancies complicated by systemic proinflammatory diseases, such as systemic lupus erythematosis, rheumatoid arthritis, and falciparum malaria (18,33,55).Human schistosomiasis, caused by three main species of tissue-invasive parasitic trematodes, infects over 200 million individuals, including ϳ40 million women of childbearing age, and remains a significant cause of morbidity and mortality in developing countries (35). Human infection with schistosomes results in the elaboration of proinflammatory cytokines, inc...

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Section: Discussionmentioning

confidence: 99%

Maternal Schistosomiasis Japonica Is Associated with Maternal, Placental, and Fetal Inflammation

Kurtis

Higashi

et al. 2011

Infect Immun

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“…In the present study, we have developed FgCA-27 ELISA, which successfully detected the 27-kDa Fasciola antigen with a detection limit of 8 ng/ml in human serum samples. The presence of Fasciola antigens in free form in the circulation of infected individuals may be attributed to continuous shedding and release of circulating antigens as a possible escape mechanism by the parasites, to reinfections, and to exposure to maternal antigens that may lead to developing tolerance rather than immunity to free antigens of natural infections (50). Moreover, the presence of high titers of specific IgG antibodies in the sera of infected individuals does not indicate a complete elimination of the pathogen; such high titers of antibodies may not neutralize all of the circulating antigens, i.e., via immune complex formation, and also, the specific IgM antibody response will not be stimulated for new infections.…”

Section: Discussionmentioning

confidence: 99%

Immunodetection of Fasciola gigantica Circulating Antigen in Sera of Infected Individuals for Laboratory Diagnosis of Human Fascioliasis

Attallah¹,

Bughdadi

El-Shazly

et al. 2013

Clin. Vaccine Immunol.

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c Currently, the laboratory diagnosis of human fascioliasis is based on the parasitological examination of parasite eggs in stool specimens and serological detection of specific antibodies in serum samples, which are often unreliable diagnostic approaches. Ideally, a sensitive and specific diagnostic test for Fasciola infection should be based on the detection of circulating Fasciola antigen, which implies active infection. Here, a 27-kDa-molecular-mass antigen was identified in a Fasciola gigantica adult worm antigen preparation, excretory-secretory products, and sera from F. gigantica-infected individuals, and it was not detected in antigenic extracts of other parasites and sera from noninfected individuals. The target antigen was isolated and partially characterized as a protein. Immunoperoxidase staining located the target epitope within teguments and guts of F. gigantica adult worms. The performance characteristics of a newly developed enzyme-linked immunosorbent assay (ELISA) based on F. gigantica circulating antigen detection in serum (FgCA-27 ELISA) were investigated using sera of 120 parasitologically diagnosed F. gigantica-infected individuals and 80 noninfected individuals. The area under the receiving operating characteristic (ROC) curve (AUC) for ELISA was significantly high (AUC ‫؍‬ 0.961, P < 0.0001) for discriminating Fasciola-infected and noninfected individuals. The developed assay showed high degrees of sensitivity, specificity, and efficiency (>93%), and a significant correlation (r ‫؍‬ 0.715, P < 0.0001) between antigen level and parasite egg count was shown. In conclusion, a 27-kDa Fasciola antigen was identified in sera of F. gigantica-infected individuals. A highly sensitive and specific Fasciola antigen detection assay, FgCA-27 ELISA, was developed for laboratory diagnosis of human fascioliasis.

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“…Although isolated reported studies have demonstrated direct trafficking of schistosome worms and whole eggs to the placental compartment in humans, this event appears to be relatively rare and is difficult to assess (40). Exposure and transfer of soluble worm and egg antigens across the placenta, however, is well documented and occurs in the majority of human pregnancies complicated with schistosome infection (41). We therefore utilized schistosome SEA in our experiments as a starting point for examination of the effect that schistosome infection might have on trophoblast cells.…”

Section: Figmentioning

confidence: 99%

Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

et al. 2013

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f Schistosomiasis affects nearly 40 million women of reproductive age. Many of these women are infected while pregnant and lactating. Several studies have demonstrated transplacental trafficking of schistosome antigens; however, little is known regarding how these antigens affect the developing fetus and placenta. To evaluate the impact of schistosomiasis on trophoblasts of the human placenta, we isolated primary trophoblast cells from healthy placentas delivered at term. These trophoblasts were placed in culture and treated with Schistosoma japonicum soluble egg antigens (SEA) or plasma from S. japonicum-infected pregnant women. Outcomes measured included cytokine production and activation of signal transduction pathways. Treatment of primary human trophoblast cells with SEA resulted in upregulation of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8 and the chemokine macrophage inflammatory protein 1␣ (MIP-1␣). Cytokine production in response to SEA was dose dependent and reminiscent of production in response to other proinflammatory stimuli, such as Toll-like receptor 2 (TLR2) and TLR4 agonists. In addition, the signaling pathways extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal protein kinase (JNK), p38, and NF-B were all activated by SEA in primary trophoblasts. These effects appeared to be mediated through both carbohydrate and protein epitopes of SEA. Finally, primary trophoblasts cocultured with plasma from S. japonicum-infected pregnant women produced increased levels of IL-8 compared to trophoblasts cocultured with plasma from uninfected pregnant women. We report here a direct impact of SEA on primary human trophoblast cells, which are critical for many aspects of a healthy pregnancy. Our data indicate that schistosome antigens can activate proinflammatory responses in trophoblasts, which might compromise maternal-fetal health in pregnancies complicated by schistosomiasis.

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Placental and Oral Delivery of Schistosoma Mansoni Antigen From Infected Mothers to Their Newborns and Children

Cited by 42 publications

References 18 publications

Maternal Schistosomiasis Japonica Is Associated with Maternal, Placental, and Fetal Inflammation

Maternal Schistosomiasis Japonica Is Associated with Maternal, Placental, and Fetal Inflammation

Immunodetection of Fasciola gigantica Circulating Antigen in Sera of Infected Individuals for Laboratory Diagnosis of Human Fascioliasis

Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

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