Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial

Abstract

BackgroundOffspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown.MethodsIn a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy.ResultsOf 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel.ConclusionsDespite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated.Trial registrationISRCTN: ISRCTN32849447

Effect of Maternal Schistosoma mansoni Infection and Praziquantel Treatment During Pregnancy on Schistosoma mansoni Infection and Immune Responsiveness among Offspring at Age Five Years

“…This finding is consistent with our earlier report in which we did not find significant effects of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens among the offspring, in either cord blood or at age one year [3]. Of some interest, however, was the IL-10 response to SWA.…”

“…For those who are tolerant, this may be due to induction of regulatory mechanisms, or to deletion of schistosome antigen specific cells. When the baby is sensitised in-utero , profiles of infant responses resemble the mothers' responses: mixed type one, type two cytokine responses and a prominent IL-10 response, as shown by our recent study on cord blood responses to schistosome worm (SWA) and egg (SEA) [3] and one earlier study [2]. Our study suggested a direct correlation between maternal S. mansoni infection intensity and cord blood T cell sensitisation of the offspring [3].…”

“…When the baby is sensitised in-utero , profiles of infant responses resemble the mothers' responses: mixed type one, type two cytokine responses and a prominent IL-10 response, as shown by our recent study on cord blood responses to schistosome worm (SWA) and egg (SEA) [3] and one earlier study [2]. Our study suggested a direct correlation between maternal S. mansoni infection intensity and cord blood T cell sensitisation of the offspring [3]. Thus immune responses to schistosome antigens typical of those observed in adults can be established in-utero in offspring born to schistosome-infected women.…”

“…Whole blood stimulation for cytokine responses to SWA and SEA was performed as previously described [3], [25], [26], [27]. SWA and SEA antigens were supplied by Professor David Dunne (Cambridge University, UK).…”

Schistosoma japonicum Soluble Egg Antigens Attenuate Invasion in a First Trimester Human Placental Trophoblast Model

“…Outside of pregnancy, we and others have related these responses to nutritional, hepatic and hematologic morbidities in infected individuals [43]–[46]. Surprisingly, maternal schistosomiasis during pregnancy elicits a pro-inflammatory response detectable in the neonate [8], and neonates exposed to maternal schistosomiasis during pregnancy display a more robust response to antigenic challenge and have elevated levels of antibodies against schistosome antigens at birth than their unexposed counterparts [13], [47]. Together, these results suggest that maternal schistosomiasis may influence the outcome of initial pediatric schistosome infections acquired during early childhood.…”